Trial Outcomes & Findings for Nordic Everolimus (Certican) Trial in Heart and Lung Transplantation (NCT NCT00377962)

Last Updated: 2020-07-30

Results Overview

Renal function was assessed by determining the measured glomerular filtration rate (mGFR) using creatinine ethylenediamine tetraacetic acid (Cr-EDTA) clearance or an equivalent method. A positive change score indicates improved renal function.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

282 participants

Primary outcome timeframe

Baseline to Month 12

Results posted on

2020-07-30

Participant Flow

This was a 12-month study in maintenance heart and lung transplant patients with a follow-up period of an additional 12 months. Results to 24 months are presented. Patients were randomized to continue their current calcineurin inhibitors (CNI) based regimen or to start everolimus with reduction of CNI blood levels.

Participant milestones

Participant milestones
Measure	Everolimus + CNI Reduction Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice	Control CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.
Core Study: 0-12 Months STARTED	140	142
Core Study: 0-12 Months COMPLETED	112	133
Core Study: 0-12 Months NOT COMPLETED	28	9
Extension Study: 12-24 Months STARTED	108	127
Extension Study: 12-24 Months COMPLETED	98	123
Extension Study: 12-24 Months NOT COMPLETED	10	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Everolimus + CNI Reduction Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice	Control CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.
Core Study: 0-12 Months Adverse Event	18	2
Core Study: 0-12 Months Death	3	0
Core Study: 0-12 Months Withdrew Consent	5	2
Core Study: 0-12 Months Administrative Reason	1	1
Core Study: 0-12 Months Unspecified reasons	1	4
Extension Study: 12-24 Months Death	1	1
Extension Study: 12-24 Months Adverse Event	8	0
Extension Study: 12-24 Months Abnormal laboratory value	1	0
Extension Study: 12-24 Months Unspecified reason	0	3

Baseline Characteristics

Nordic Everolimus (Certican) Trial in Heart and Lung Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Everolimus + CNI Reduction n=140 Participants Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice	Control n=142 Participants CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.	Total n=282 Participants Total of all reporting groups
Age, Continuous	59.2 years STANDARD_DEVIATION 9.5 • n=93 Participants	56.4 years STANDARD_DEVIATION 10.7 • n=4 Participants	57.8 years STANDARD_DEVIATION 9.96 • n=27 Participants
Sex: Female, Male Female	37 Participants n=93 Participants	40 Participants n=4 Participants	77 Participants n=27 Participants
Sex: Female, Male Male	103 Participants n=93 Participants	102 Participants n=4 Participants	205 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline to Month 12

Population: Intent-to-treat (ITT) population: All randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment.

Outcome measures

Outcome measures
Measure	Everolimus + CNI Reduction n=114 Participants Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice	Control n=132 Participants CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.
Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to Month 12 Month 12	53.2 mL/min Standard Deviation 15.7	47.5 mL/min Standard Deviation 16.1
Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to Month 12 Baseline	48.6 mL/min Standard Deviation 15.1	48.0 mL/min Standard Deviation 13.2
Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to Month 12 Change from Baseline	4.6 mL/min Standard Deviation 10.4	-0.5 mL/min Standard Deviation 9.0

SECONDARY outcome

Timeframe: Baseline to end of study (Month 24)

Population: Intent-to-treat (ITT) population: All randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment.

Outcome measures

Outcome measures
Measure	Everolimus + CNI Reduction n=103 Participants Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice	Control n=119 Participants CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.
Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to End of Study (Month 24) Change	3.2 mL/min Standard Deviation 12.3	-2.4 mL/min Standard Deviation 9.0
Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to End of Study (Month 24) Month 0	49.3 mL/min Standard Deviation 14.7	49.1 mL/min Standard Deviation 13.0
Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to End of Study (Month 24) Month 24	52.5 mL/min Standard Deviation 16.4	46.8 mL/min Standard Deviation 15.2

SECONDARY outcome

Timeframe: Baseline to end of study (Month 24)

Population: Intent-to-treat (ITT) population: All randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment.

Renal function was assessed by determining serum creatinine using standard laboratory methods. A positive change score indicates improved renal function.

Outcome measures

Outcome measures
Measure	Everolimus + CNI Reduction n=114 Participants Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice	Control n=132 Participants CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.
Change in Serum Creatinine From Baseline to End of Study (Month 24) Month 0	126 μmol/L Standard Deviation 30	129 μmol/L Standard Deviation 29
Change in Serum Creatinine From Baseline to End of Study (Month 24) Change	0 μmol/L Standard Deviation 53	3 μmol/L Standard Deviation 23
Change in Serum Creatinine From Baseline to End of Study (Month 24) Month 24	126 μmol/L Standard Deviation 64	132 μmol/L Standard Deviation 37

SECONDARY outcome

Timeframe: Month 12 to end of study (Month 24)

Population: Intent-to-treat (ITT) population: All randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment.

Biopsy-proved acute rejection was defined as a treated acute rejection confirmed by biopsy, graded locally according to the International Society for Heart \& Lung Transplantation (ISHLT) criteria. A treated acute rejection was defined as an acute rejection clinically suspected, whether biopsy-proven or not, which had been treated and confirmed by the investigator according to the response to therapy.

Outcome measures

Outcome measures
Measure	Everolimus + CNI Reduction n=108 Participants Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice	Control n=127 Participants CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.
Number of Patients With Biopsy-proven Acute Rejection From Month 12 to End of Study (Month 24)	6 Participants	5 Participants

SECONDARY outcome

Timeframe: Month 12 to end of study (Month 24)

Population: Intent-to-treat (ITT) population: All randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment.

Number of patients not alive and number of patients with loss of their graft.

Outcome measures

Outcome measures
Measure	Everolimus + CNI Reduction n=108 Participants Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice	Control n=127 Participants CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.
Number of Patients Who Died and Number of Patients With Graft Loss From Month 12 to End of Study (Month 24) Death	3 Participants	0 Participants
Number of Patients Who Died and Number of Patients With Graft Loss From Month 12 to End of Study (Month 24) Graft Loss	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Month 12 to end of study (Month 24)

Population: The intent-to-treat (ITT) population consisted of all patients as randomized, who were given at least one dose of study drug and had at least one post-baseline assessment. (Extension study)

Outcome measures

Outcome measures
Measure	Everolimus + CNI Reduction n=108 Participants Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice	Control n=127 Participants CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.
Number of Patients in Need of Dialysis From Month 12 to End of Study (Month 24)	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline to end of study (Month 24)

Population: Patients in the lung transplant subgroup of the intent-to-treat (ITT) population which included all randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment.

Forced expiratory volume in 1 second (FEV1) was measured by spirometry conducted according to internationally accepted standards. FEV1 is the volume delivered in the first second of a forced vital capacity (FVC) maneuver. A positive change score indicates improved lung function.

Outcome measures

Outcome measures
Measure	Everolimus + CNI Reduction n=36 Participants Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice	Control n=40 Participants CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.
Change in Forced Expiratory Volume in 1 Second (FEV1) From Baseline to End of Study (Month 24) in the Lung Transplant Subgroup	-0.2 Liters Standard Deviation 0.2	-0.1 Liters Standard Deviation 0.2

SECONDARY outcome

Timeframe: Baseline to end of study (Month 24)

Forced vital capacity (FVC) was measured by spirometry conducted according to internationally accepted standards. FVC is the volume delivered during an expiration made as forcefully and completely as possible starting from full inspiration. A positive change score indicates improved lung function.

Outcome measures

Outcome measures
Measure	Everolimus + CNI Reduction n=36 Participants Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice	Control n=40 Participants CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.
Change in Forced Vital Capacity (FVC) From Baseline to End of Study (Month 24) in the Lung Transplant Subgroup	-0.2 Liters Standard Deviation 0.3	-0.1 Liters Standard Deviation 0.4

SECONDARY outcome

Timeframe: Baseline to end of study (Month 24)

Population: Patients in the heart transplant subgroup of the intent-to-treat (ITT) population which included all randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment.

Left ventricular function was assessed by echocardiography which was performed according to local routine practice. Echocardiography parameters were left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), interventricular septal wall thickness (IVSTd), and posterior wall thickness (PWTd). A positive change score indicates improved left ventricular function.

Outcome measures

Outcome measures
Measure	Everolimus + CNI Reduction n=56 Participants Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice	Control n=73 Participants CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.
Change in Left Ventricular Function (Diameter and Thickness Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup LVEDD	-0.1 cm Standard Deviation 0.8	-0.0 cm Standard Deviation 0.4
Change in Left Ventricular Function (Diameter and Thickness Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup LVESD	0.1 cm Standard Deviation 0.7	0.1 cm Standard Deviation 0.6
Change in Left Ventricular Function (Diameter and Thickness Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup IVSTd	-0.4 cm Standard Deviation 2.4	-0.1 cm Standard Deviation 1.2
Change in Left Ventricular Function (Diameter and Thickness Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup PWTd	-0.5 cm Standard Deviation 2.1	-0.1 cm Standard Deviation 1.1

SECONDARY outcome

Timeframe: Baseline to end of study (Month 24)

Left ventricular function was assessed by echocardiography which was performed according to local routine practice. Echocardiography parameters were filling fraction (FF) and ejection fraction (EF). A positive change score indicates improved left ventricular function.

Outcome measures

Outcome measures
Measure	Everolimus + CNI Reduction n=59 Participants Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice	Control n=71 Participants CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.
Change in Left Ventricular Function (Filling and Ejection Fraction Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup EF	-0.6 percentage Standard Deviation 8.5	0.1 percentage Standard Deviation 7.9
Change in Left Ventricular Function (Filling and Ejection Fraction Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup FF	0 percentage Standard Deviation 1	0 percentage Standard Deviation 1

SECONDARY outcome

Timeframe: Baseline to end of study (Month 24)

Population: Intent-to-treat (ITT) population: All randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment.

Outcome measures

Outcome measures
Measure	Everolimus + CNI Reduction n=108 Participants Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice	Control n=127 Participants CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.
Mean Days of Hospitalization From Baseline to End of Study (Month 24)	8.5 Days Standard Deviation 7.4	16.2 Days Standard Deviation 19.3

SECONDARY outcome

Timeframe: Month 12 to end of study (Month 24)

Population: Intent-to-treat (ITT) population: All randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment.

Outcome measures

Outcome measures
Measure	Everolimus + CNI Reduction n=108 Participants Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice	Control n=127 Participants CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.
Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) Total discontinued due to AE(s)	8 Participants	0 Participants
Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) Pulmonary embolism	2 Participants	0 Participants
Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) Skin problems	1 Participants	0 Participants
Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) Hypercholesterolemia	1 Participants	0 Participants
Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) Stroke	1 Participants	0 Participants
Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) Muscular pain	1 Participants	0 Participants
Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) Diarrhea	1 Participants	0 Participants
Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) Edema	1 Participants	0 Participants

Adverse Events

Control: 12 Month Heart

Serious events: 23 serious events

Other events: 48 other events

Deaths: 0 deaths

Everolimus + CNI Reduction: 12 Month Heart

Serious events: 40 serious events

Other events: 75 other events

Deaths: 0 deaths

Control: 12 Month Lung

Serious events: 17 serious events

Other events: 33 other events

Deaths: 0 deaths

Everolimus+CNI Reduction: 12 Month Lung

Serious events: 25 serious events

Other events: 42 other events

Deaths: 0 deaths

Control: 24 Month Heart

Serious events: 31 serious events

Other events: 33 other events

Deaths: 0 deaths

Everolimus + CNI Reduction: 24 Month Heart

Serious events: 25 serious events

Other events: 29 other events

Deaths: 0 deaths

Control: 24 Month Lung

Serious events: 21 serious events

Other events: 21 other events

Deaths: 0 deaths

Everolimus + CNI Reduction: 24 Month Lung

Serious events: 16 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Control: 12 Month Heart n=96 participants at risk Subgroup of "Control" group with heart patients at 12 months. CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.	Everolimus + CNI Reduction: 12 Month Heart n=94 participants at risk Subgroup of "everolimus + CNI reduction" group with heart patients at 12 months. Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%, upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice.	Control: 12 Month Lung n=46 participants at risk Subgroup of "control" group with lung patients at 12 months. CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.	Everolimus+CNI Reduction: 12 Month Lung n=46 participants at risk Subgroup of "everolimus + CNI reduction" group with lung patients at 12 months. Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%, upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice.	Control: 24 Month Heart n=86 participants at risk Subgroup of "Control" group with heart patients at 24 months. CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.	Everolimus + CNI Reduction: 24 Month Heart n=69 participants at risk Subgroup of "everolimus + CNI reduction" group with heart patients at 24 months. Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%, upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice.	Control: 24 Month Lung n=41 participants at risk Subgroup of "Control" group with lung patients at 24 months. CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.	Everolimus + CNI Reduction: 24 Month Lung n=39 participants at risk Subgroup of "everolimus + CNI reduction" group with lung patients at 24 months. Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%, upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice.
Infections and infestations Ear infection NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Epididymitis NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Blood and lymphatic system disorders Anaemia NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Cardiac disorders Angina pectoris	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Cardiac disorders Aortic valve stenosis	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Cardiac disorders Atrial fibrillation	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Cardiac disorders Atrial flutter	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Cardiac disorders Atrial tachycardia	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Cardiac disorders Cardiac failure NOS	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Cardiac disorders Coronary artery atheroma haemorrhage	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Cardiac disorders Coronary artery disease NOS	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Cardiac disorders Oedema NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	3.2% 3/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Cardiac disorders Pulmonary oedema NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Cardiac disorders Right ventricular failure	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Cardiac disorders Supraventricular tachycardia	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Endocrine disorders Hyperthyroidism	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Gastrointestinal disorders Abdominal pain NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Gastrointestinal disorders Acute abdomen	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Gastrointestinal disorders Appendicitis	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Gastrointestinal disorders Diarrhoea NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.1% 2/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Gastrointestinal disorders Diverticulitis NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Gastrointestinal disorders Food poisoning NOS	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Gastrointestinal disorders Gastric ulcer	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Gastrointestinal disorders Gastric ulcer perforation	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Gastrointestinal disorders Gastrointestinal haemorrhage NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Gastrointestinal disorders Ileus	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Gastrointestinal disorders Inguinal hernia NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Gastrointestinal disorders Nausea	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Gastrointestinal disorders Pancreatitis NOS	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Gastrointestinal disorders Peptic ulcer	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Gastrointestinal disorders Rectal disorder NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Gastrointestinal disorders Vomiting NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.1% 2/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
General disorders Chest pain	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
General disorders Compartment syndrome	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
General disorders Death NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.6% 1/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
General disorders Fatigue	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
General disorders Haemorrhage NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
General disorders Malaise	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
General disorders Pain NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
General disorders Pyrexia	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	3.2% 3/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Hepatobiliary disorders Cholelithiasis	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Immune system disorders Graft rejection	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Immune system disorders Heart transplant rejection	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Immune system disorders Hypersensitivity NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Brain abscess NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Bronchitis NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Bronchitis acute NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.3% 2/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.6% 1/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Cholecystitis acute NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Cystitis NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Cytomegalovirus infection	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Erysipelas	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Gastroenteritis NOS	2.1% 2/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.3% 2/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.9% 2/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Herpes simplex	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Herpes zoster	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.1% 2/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.6% 1/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Infection NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Influenza	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.6% 1/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Lobar pneumonia NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Localised infection	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Lower respiratory tract infection NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.6% 1/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Nasopharyngitis	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Pneumonia NOS	3.1% 3/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	7.4% 7/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	6.5% 3/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	13.0% 6/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.3% 2/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	17.1% 7/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	12.8% 5/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Pneumonia aspergilla	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Pseudomonas aeruginosa infection NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.3% 2/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Pyelonephritis NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Sepsis NOS	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Sinusitis NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Upper respiratory tract infection NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.3% 2/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Urinary tract infection NOS	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	3.2% 3/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.9% 2/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Injury, poisoning and procedural complications Animal bite	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.6% 1/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Injury, poisoning and procedural complications Forearm fracture	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Injury, poisoning and procedural complications Fracture NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Injury, poisoning and procedural complications Hand fracture	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Injury, poisoning and procedural complications Head injury	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Injury, poisoning and procedural complications Leg fracture	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Investigations Arteriogram coronary	2.1% 2/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Investigations Biopsy lung	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Investigations Blood creatinine increased	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Investigations Lung function abnormal	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Investigations Lung function decreased	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Investigations Lymphocyte morphology NOS abnormal	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Investigations Pericardial drainage	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Investigations Weight decreased	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Metabolism and nutrition disorders Gout	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Metabolism and nutrition disorders Malnutrition NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.6% 1/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Musculoskeletal and connective tissue disorders Arthritis NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Musculoskeletal and connective tissue disorders Back pain	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Musculoskeletal and connective tissue disorders Bursitis	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Musculoskeletal and connective tissue disorders Intervertebral disc prolapse	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Musculoskeletal and connective tissue disorders Localised osteoarthritis	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Musculoskeletal and connective tissue disorders Muscle atrophy	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Musculoskeletal and connective tissue disorders Sciatica	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.9% 2/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign adrenal neoplasm NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bowen's disease	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer female NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Carcinoma NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lip neoplasm malignant stage unspecified	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer stage unspecified (exc metas	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma stage IV	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin carcinoma NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	3.1% 3/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	5.1% 2/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Nervous system disorders Burning sensation NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Nervous system disorders Cerebrovascular accident NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Nervous system disorders Dizziness (exc vertigo)	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.1% 2/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Nervous system disorders Epilepsy NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Nervous system disorders Haemorrhagic stroke	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Nervous system disorders Migraine NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Nervous system disorders Monoparesis	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Nervous system disorders Restless leg syndrome	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Nervous system disorders Syncope	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Nervous system disorders Syncope aggravated	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Psychiatric disorders Confusion	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Renal and urinary disorders Fluid retention	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Renal and urinary disorders Nephropathy NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Renal and urinary disorders Oliguria	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Renal and urinary disorders Renal failure NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.1% 2/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Renal and urinary disorders Renal impairment NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.6% 1/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Reproductive system and breast disorders Ovarian cyst	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.6% 1/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Reproductive system and breast disorders Uterine prolapse	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Respiratory, thoracic and mediastinal disorders Asthma NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Respiratory, thoracic and mediastinal disorders Bronchostenosis	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Respiratory, thoracic and mediastinal disorders Dyspnoea NOS	2.1% 2/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.1% 2/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.3% 2/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Respiratory, thoracic and mediastinal disorders Excessive bronchial secretion	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.9% 2/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Respiratory, thoracic and mediastinal disorders Mediastinal emphysema	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Respiratory, thoracic and mediastinal disorders Obliterative bronchiolitis	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.3% 2/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	14.6% 6/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.6% 1/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Respiratory, thoracic and mediastinal disorders Pneumothorax NOS	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.6% 1/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Respiratory, thoracic and mediastinal disorders Respiratory failure (exc neonatal)	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Skin and subcutaneous tissue disorders Angioneurotic oedema	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Skin and subcutaneous tissue disorders Dermatitis NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Skin and subcutaneous tissue disorders Diabetic foot ulcer	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Surgical and medical procedures Angioplasty	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.9% 2/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Surgical and medical procedures Cholecystectomy	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Surgical and medical procedures Facial lesion excision	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Surgical and medical procedures Hip arthroplasty	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Surgical and medical procedures Leg amputation	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Surgical and medical procedures Operation NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Surgical and medical procedures Suture removal	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Vascular disorders Arterial stenosis NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Vascular disorders Arteriosclerosis	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Vascular disorders Cerebral artery thrombosis	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Vascular disorders Hypertension aggravated	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Vascular disorders Intracranial haemorrhage NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Vascular disorders Phlebitis NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Vascular disorders Postural hypotension	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Vascular disorders Pulmonary embolism	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.3% 2/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.3% 2/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.9% 2/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.6% 1/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Vascular disorders Pulmonary hypertension NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Vascular disorders Subarachnoid haemorrhage NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Vascular disorders Transient ischaemic attack	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Vascular disorders Venous thrombosis NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Vascular disorders Venous thrombosis deep limb	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.1% 2/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.6% 1/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.

Other adverse events

Other adverse events
Measure	Control: 12 Month Heart n=96 participants at risk Subgroup of "Control" group with heart patients at 12 months. CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.	Everolimus + CNI Reduction: 12 Month Heart n=94 participants at risk Subgroup of "everolimus + CNI reduction" group with heart patients at 12 months. Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%, upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice.	Control: 12 Month Lung n=46 participants at risk Subgroup of "control" group with lung patients at 12 months. CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.	Everolimus+CNI Reduction: 12 Month Lung n=46 participants at risk Subgroup of "everolimus + CNI reduction" group with lung patients at 12 months. Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%, upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice.	Control: 24 Month Heart n=86 participants at risk Subgroup of "Control" group with heart patients at 24 months. CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.	Everolimus + CNI Reduction: 24 Month Heart n=69 participants at risk Subgroup of "everolimus + CNI reduction" group with heart patients at 24 months. Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%, upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice.	Control: 24 Month Lung n=41 participants at risk Subgroup of "Control" group with lung patients at 24 months. CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.	Everolimus + CNI Reduction: 24 Month Lung n=39 participants at risk Subgroup of "everolimus + CNI reduction" group with lung patients at 24 months. Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%, upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice.
Blood and lymphatic system disorders Leucopenia NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	8.5% 8/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	17.4% 8/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.6% 1/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Cardiac disorders Oedema NOS	10.4% 10/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	25.5% 24/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	6.5% 3/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	30.4% 14/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	10.5% 9/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	5.8% 4/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.9% 2/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	12.8% 5/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Congenital, familial and genetic disorders Epidermal naevus	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	5.1% 2/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Gastrointestinal disorders Abdominal pain upper	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	6.5% 3/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	7.3% 3/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Gastrointestinal disorders Diarrhoea NOS	4.2% 4/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	16.0% 15/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	6.5% 3/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	15.2% 7/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	5.8% 4/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	7.7% 3/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Gastrointestinal disorders Gastritis NOS	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	5.1% 2/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Gastrointestinal disorders Mouth ulceration	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	10.9% 5/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Gastrointestinal disorders Nausea	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.3% 4/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.3% 2/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.3% 2/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	5.1% 2/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
General disorders Fall	2.1% 2/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.3% 2/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	5.1% 2/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
General disorders Fatigue	5.2% 5/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	6.4% 6/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.3% 2/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.3% 2/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
General disorders Pyrexia	6.2% 6/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.3% 2/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Bronchitis NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	5.3% 5/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	6.5% 3/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.3% 2/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.9% 2/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	5.1% 2/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Infection NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	3.2% 3/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	3.5% 3/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.9% 2/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.9% 2/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	5.1% 2/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Influenza	5.2% 5/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.1% 2/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.3% 2/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.9% 2/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.6% 1/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Nasopharyngitis	15.6% 15/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	19.1% 18/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	26.1% 12/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	23.9% 11/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	14.0% 12/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	10.1% 7/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	17.1% 7/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	20.5% 8/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Pneumonia NOS	5.2% 5/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	3.2% 3/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.3% 2/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	10.9% 5/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	7.7% 3/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Upper respiratory tract infection NOS	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.1% 2/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	13.0% 6/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	19.6% 9/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.3% 2/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.9% 2/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	9.8% 4/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	15.4% 6/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Infections and infestations Urinary tract infection NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	3.2% 3/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	6.5% 3/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	8.7% 4/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.9% 2/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	7.7% 3/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Investigations Blood creatinine increased	2.1% 2/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	5.1% 2/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Metabolism and nutrition disorders Hypercholesterolaemia	4.2% 4/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	6.5% 3/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	13.0% 6/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.9% 2/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	5.1% 2/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.1% 1/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	8.7% 4/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	5.1% 2/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Musculoskeletal and connective tissue disorders Arthralgia	5.2% 5/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	6.4% 6/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.3% 2/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	6.5% 3/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.6% 1/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Musculoskeletal and connective tissue disorders Arthritis NOS	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	6.5% 3/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.6% 1/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Musculoskeletal and connective tissue disorders Myalgia	3.1% 3/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	7.4% 7/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.3% 2/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Musculoskeletal and connective tissue disorders Pain in limb	1.0% 1/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	5.3% 5/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.3% 2/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Nervous system disorders Headache NOS	7.3% 7/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	7.4% 7/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	6.5% 3/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	10.9% 5/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.2% 1/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.6% 1/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Respiratory, thoracic and mediastinal disorders Cough	3.1% 3/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	5.3% 5/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	6.5% 3/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	6.5% 3/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.3% 3/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.6% 1/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Respiratory, thoracic and mediastinal disorders Excessive bronchial secretion	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	5.1% 2/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Skin and subcutaneous tissue disorders Acne NOS	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	11.7% 11/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.6% 1/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Vascular disorders Hypertension NOS	5.2% 5/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.3% 4/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	8.7% 4/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	13.0% 6/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	0.00% 0/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.3% 3/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	4.9% 2/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	7.7% 3/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.
Vascular disorders Hypertension aggravated	0.00% 0/96 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	5.3% 5/94 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.2% 1/46 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	3.5% 3/86 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	1.4% 1/69 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.4% 1/41 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.	2.6% 1/39 • 24 months Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862 778-8300

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER