Trial Outcomes & Findings for Safety and Efficacy Study of the Medtronic CoreValve® System in the Treatment of Severe, Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI). (NCT NCT01586910)

Last Updated: 2025-10-28

Results Overview

All-cause mortality: all deaths from any cause after valve intervention. This includes all cardiovascular and non-cardiovascular deaths. Disabling Stroke: a modified rankin (mRS) score of 2 or more at 90 days and an increase in at least one mRS category from an individual's pre-strike baseline.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

Target enrollment

1746 participants

Primary outcome timeframe

24 months

Results posted on

2025-10-28

Participant Flow

Participant milestones

Participant milestones
Measure	Medtronic CoreValve® System TAVI Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR Surgical Aortic Valve Replacement (SAVR)
Overall Study STARTED	879	867
Overall Study COMPLETED	864	796
Overall Study NOT COMPLETED	15	71

Reasons for withdrawal

Reasons for withdrawal
Measure	Medtronic CoreValve® System TAVI Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR Surgical Aortic Valve Replacement (SAVR)
Overall Study Death	4	4
Overall Study Withdrawal by Subject	6	43
Overall Study Physician withdrew Subject	5	24

Baseline Characteristics

Data from three race categories (Asian, Black/African American/ Hispanic or Latino Ethnicity) were collected in the study.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Medtronic CoreValve® System TAVI n=864 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=796 Participants Surgical Aortic Valve Replacement (SAVR)	Total n=1660 Participants Total of all reporting groups
Age, Continuous	79.9 years STANDARD_DEVIATION 6.2 • n=864 Participants	79.7 years STANDARD_DEVIATION 6.1 • n=796 Participants	79.8 years STANDARD_DEVIATION 6.2 • n=1660 Participants
Sex: Female, Male Female	366 Participants n=864 Participants	358 Participants n=796 Participants	724 Participants n=1660 Participants
Sex: Female, Male Male	498 Participants n=864 Participants	438 Participants n=796 Participants	936 Participants n=1660 Participants
Race/Ethnicity, Customized Asian	7 Participants n=43 Participants • Data from three race categories (Asian, Black/African American/ Hispanic or Latino Ethnicity) were collected in the study.	6 Participants n=50 Participants • Data from three race categories (Asian, Black/African American/ Hispanic or Latino Ethnicity) were collected in the study.	13 Participants n=93 Participants • Data from three race categories (Asian, Black/African American/ Hispanic or Latino Ethnicity) were collected in the study.
Race/Ethnicity, Customized Black/African American	18 Participants n=43 Participants • Data from three race categories (Asian, Black/African American/ Hispanic or Latino Ethnicity) were collected in the study.	21 Participants n=50 Participants • Data from three race categories (Asian, Black/African American/ Hispanic or Latino Ethnicity) were collected in the study.	39 Participants n=93 Participants • Data from three race categories (Asian, Black/African American/ Hispanic or Latino Ethnicity) were collected in the study.
Race/Ethnicity, Customized Hispanic or Latino Ethnicity	18 Participants n=43 Participants • Data from three race categories (Asian, Black/African American/ Hispanic or Latino Ethnicity) were collected in the study.	23 Participants n=50 Participants • Data from three race categories (Asian, Black/African American/ Hispanic or Latino Ethnicity) were collected in the study.	41 Participants n=93 Participants • Data from three race categories (Asian, Black/African American/ Hispanic or Latino Ethnicity) were collected in the study.
NYHA Class I	0 Participants n=864 Participants	0 Participants n=796 Participants	0 Participants n=1660 Participants
NYHA Class II	344 Participants n=864 Participants	333 Participants n=796 Participants	677 Participants n=1660 Participants
NYHA Class III	472 Participants n=864 Participants	411 Participants n=796 Participants	883 Participants n=1660 Participants
NYHA Class IV	48 Participants n=864 Participants	52 Participants n=796 Participants	100 Participants n=1660 Participants
Body Surface Area	1.9 meters squared STANDARD_DEVIATION 0.2 • n=864 Participants	1.9 meters squared STANDARD_DEVIATION 0.2 • n=796 Participants	1.9 meters squared STANDARD_DEVIATION 0.2 • n=1660 Participants
STS Score	4.4 % risk of mortality STANDARD_DEVIATION 1.5 • n=864 Participants	4.5 % risk of mortality STANDARD_DEVIATION 1.6 • n=796 Participants	4.5 % risk of mortality STANDARD_DEVIATION 1.6 • n=1660 Participants
Logistic EuroSCORE	11.9 percentage of predicted mortality STANDARD_DEVIATION 7.6 • n=864 Participants • Data missing for 1 SAVR subject.	11.6 percentage of predicted mortality STANDARD_DEVIATION 8.0 • n=795 Participants • Data missing for 1 SAVR subject.	11.8 percentage of predicted mortality STANDARD_DEVIATION 7.8 • n=1659 Participants • Data missing for 1 SAVR subject.

PRIMARY outcome

Timeframe: 24 months

Population: Participant Population= Consisted of all randomized subjects with an attempted implant procedure.

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=864 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=796 Participants Surgical Aortic Valve Replacement (SAVR)
All-cause Mortality or Disabling Stroke Rate Expressed as a Posterior Probability	12.6 Percentage of Participants Interval 10.2 to 15.3	14.0 Percentage of Participants Interval 11.4 to 17.0

SECONDARY outcome

Timeframe: 30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete.

Population: Participant Population= Consisted of all randomized subjects with an attempted implant procedure.

MACCE is defined as a composite of: * All-cause death * Myocardial infarction (MI) * All stroke, and * Reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve)

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=864 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=796 Participants Surgical Aortic Valve Replacement (SAVR)
Percentage of Participants With Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) 30 days	5.7 percentage of participants	7.3 percentage of participants
Percentage of Participants With Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) 6 months	9.5 percentage of participants	10.7 percentage of participants
Percentage of Participants With Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) 12 months	13.0 percentage of participants	13.0 percentage of participants
Percentage of Participants With Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) 18 months	15.6 percentage of participants	14.8 percentage of participants
Percentage of Participants With Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) 24 months	18.5 percentage of participants	18.2 percentage of participants

SECONDARY outcome

Timeframe: 30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete.

Population: Participant Population= Consisted of all randomized subjects with an attempted implant procedure.

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=864 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=796 Participants Surgical Aortic Valve Replacement (SAVR)
Percentage of Participants With Individual MACCE Components 30 day All Cause Mortality	2.1 percentage of participants	1.6 percentage of participants
Percentage of Participants With Individual MACCE Components 30 day MI	0.8 percentage of participants	0.9 percentage of participants
Percentage of Participants With Individual MACCE Components 30 day Stroke	3.3 percentage of participants	5.4 percentage of participants
Percentage of Participants With Individual MACCE Components 30 day Reintervention	0.8 percentage of participants	0.1 percentage of participants
Percentage of Participants With Individual MACCE Components 6 month All Cause Mortality	4.2 percentage of participants	4.7 percentage of participants
Percentage of Participants With Individual MACCE Components 6 month MI	1.2 percentage of participants	1.4 percentage of participants
Percentage of Participants With Individual MACCE Components 6 month Stroke	4.6 percentage of participants	6.6 percentage of participants
Percentage of Participants With Individual MACCE Components 6 month Reintervention	1.8 percentage of participants	0.3 percentage of participants
Percentage of Participants With Individual MACCE Components 12 month All Cause Mortality	6.5 percentage of participants	6.7 percentage of participants
Percentage of Participants With Individual MACCE Components 12 month MI	1.9 percentage of participants	1.4 percentage of participants
Percentage of Participants With Individual MACCE Components 12 month Stroke	5.2 percentage of participants	6.9 percentage of participants
Percentage of Participants With Individual MACCE Components 12 month Reintervention	2.0 percentage of participants	0.5 percentage of participants
Percentage of Participants With Individual MACCE Components 18 month All Cause Mortality	8.5 percentage of participants	7.9 percentage of participants
Percentage of Participants With Individual MACCE Components 18 month MI	2.2 percentage of participants	1.8 percentage of participants
Percentage of Participants With Individual MACCE Components 18 month Stroke	5.7 percentage of participants	7.5 percentage of participants
Percentage of Participants With Individual MACCE Components 18 month Reintervention	2.4 percentage of participants	0.5 percentage of participants
Percentage of Participants With Individual MACCE Components 24 month All Cause Mortality	11.5 percentage of participants	10.5 percentage of participants
Percentage of Participants With Individual MACCE Components 24 month MI	2.7 percentage of participants	2.2 percentage of participants
Percentage of Participants With Individual MACCE Components 24 month Stroke	6.0 percentage of participants	8.5 percentage of participants
Percentage of Participants With Individual MACCE Components 24 month Reintervention	2.4 percentage of participants	0.5 percentage of participants

SECONDARY outcome

Timeframe: 30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete.

Population: Participant Population= Consisted of all randomized subjects with an attempted implant procedure.

Major Adverse Events (MAE) include all death, MI, all stroke, reintervention, cardiac perforation, cardiac tamponade, cardiogenic shock, valve malpositioning, prosthetic valve dysfunction, acute kidney injury, major vascular complication, life threatening or disabling bleed, major bleed, and valve endocarditis.

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=864 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=796 Participants Surgical Aortic Valve Replacement (SAVR)
Percentage of Participants With Major Adverse Events (MAE) 30 days	23.7 percentage of participants	30.3 percentage of participants
Percentage of Participants With Major Adverse Events (MAE) 6 months	28.5 percentage of participants	33.6 percentage of participants
Percentage of Participants With Major Adverse Events (MAE) 12 months	33.0 percentage of participants	35.8 percentage of participants
Percentage of Participants With Major Adverse Events (MAE) 18 months	36.6 percentage of participants	38.4 percentage of participants
Percentage of Participants With Major Adverse Events (MAE) 24 months	40.0 percentage of participants	41.8 percentage of participants

SECONDARY outcome

Timeframe: 30 day, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete.

Population: Participant Population= Consisted of all randomized subjects with an attempted implant procedure.

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=864 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=796 Participants Surgical Aortic Valve Replacement (SAVR)
Percentage of Participants With Conduction Disturbance Requiring Permanent Pacemaker Implantation 30 days	25.6 percentage of participants	6.5 percentage of participants
Percentage of Participants With Conduction Disturbance Requiring Permanent Pacemaker Implantation 6 months	27.2 percentage of participants	7.6 percentage of participants
Percentage of Participants With Conduction Disturbance Requiring Permanent Pacemaker Implantation 12 months	28.3 percentage of participants	8.6 percentage of participants
Percentage of Participants With Conduction Disturbance Requiring Permanent Pacemaker Implantation 18 months	30.1 percentage of participants	9.2 percentage of participants
Percentage of Participants With Conduction Disturbance Requiring Permanent Pacemaker Implantation 24 months	30.9 percentage of participants	9.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline to 30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete.

Population: Participant Population= Consisted of all randomized subjects with an attempted implant procedure.

Change from baseline (continuous variable). A positive number corresponds to NYHA worsening; a negative number corresponds to NYHA improvement. New York Heart Association (NYHA) Classification: Class I: Subjects with cardiac disease but without resulting limitations of physical activity. Class I: Subjects with cardiac disease resulting in slight limitation of physical activity. Class III: Subjects with cardiac disease resulting in marked limitation of physical activity. Class IV: Subjects with cardiac disease resulting in inability to carry on any physical activity without discomfort.

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=864 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=796 Participants Surgical Aortic Valve Replacement (SAVR)
Change in NYHA Class From Baseline 30 day	-1.2 units on a scale Standard Deviation 0.8	-1.0 units on a scale Standard Deviation 0.9
Change in NYHA Class From Baseline 6 month	-1.3 units on a scale Standard Deviation 0.8	-1.3 units on a scale Standard Deviation 0.8
Change in NYHA Class From Baseline 12 month	-1.3 units on a scale Standard Deviation 0.8	-1.3 units on a scale Standard Deviation 0.8
Change in NYHA Class From Baseline 18 month	-1.2 units on a scale Standard Deviation 0.8	-1.2 units on a scale Standard Deviation 0.8
Change in NYHA Class From Baseline 24 month	-1.2 units on a scale Standard Deviation 0.8	-1.2 units on a scale Standard Deviation 0.8

SECONDARY outcome

Timeframe: From baseline to 30 days, baseline to 12 months, and baseline to 24 months

Population: Participant Population= Consisted of all randomized subjects with an attempted implant procedure.

Change in distance walked during 6MWT from baseline

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=864 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=796 Participants Surgical Aortic Valve Replacement (SAVR)
Change in Distance Walked During 6-minute Walk Test (6MWT) 30 days	35.4 meters Standard Deviation 99.2	-14.4 meters Standard Deviation 108.7
Change in Distance Walked During 6-minute Walk Test (6MWT) 12 months	37.1 meters Standard Deviation 103.5	17.8 meters Standard Deviation 102.0
Change in Distance Walked During 6-minute Walk Test (6MWT) 24 months	26.5 meters Standard Deviation 115.4	11.7 meters Standard Deviation 102.7

SECONDARY outcome

Timeframe: 12 and 24 months

Population: Participant Population= Consisted of all randomized subjects with an attempted implant procedure.

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=864 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=796 Participants Surgical Aortic Valve Replacement (SAVR)
Ratio of Days Alive Out of Hospital Versus Total Days Alive 12 months	0.96 ratio Standard Deviation 0.12	0.93 ratio Standard Deviation 0.15
Ratio of Days Alive Out of Hospital Versus Total Days Alive 24 months	0.96 ratio Standard Deviation 0.12	0.95 ratio Standard Deviation 0.15

SECONDARY outcome

Timeframe: Baseline, 30 days, 3 months, 6 months, 12 months, and 24 months. Data for 3-5 years will be posted once data is complete.

Population: Participant Population= Consisted of all randomized subjects with an attempted implant procedure.

QoL summary score change from baseline using the following measures: * Kansas City Cardiomyopathy Questionnaire (KCCQ): Quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. * 36 Item Short Form Health Survey (SF-36): Measures functional health and well-being. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. * European QoL (EQ-5D): Measures 5 domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that can be converted to utilities using an algorithm. Utilities range from 0 to 1, with 1 representing perfect health, and 0 corresponding to the worst imaginable health state.

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=864 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=796 Participants Surgical Aortic Valve Replacement (SAVR)
Quality of Life (QoL) Change From Baseline 12 month SF-36-Physical	5.2 units on a scale Standard Deviation 9.9	5.2 units on a scale Standard Deviation 10.2
Quality of Life (QoL) Change From Baseline 3 month EQ-5D	0.06 units on a scale Standard Deviation 0.18	0.05 units on a scale Standard Deviation 0.18
Quality of Life (QoL) Change From Baseline 30 day KCCQ- Overall	18.4 units on a scale Standard Deviation 22.8	5.9 units on a scale Standard Deviation 27.0
Quality of Life (QoL) Change From Baseline 30 day KCCQ- Clinical	14.9 units on a scale Standard Deviation 21.2	4.0 units on a scale Standard Deviation 26.0
Quality of Life (QoL) Change From Baseline 30 day SF-36-Physical	5.7 units on a scale Standard Deviation 10.4	-1.1 units on a scale Standard Deviation 11.0
Quality of Life (QoL) Change From Baseline 30 day SF-36-Mental	2.6 units on a scale Standard Deviation 12.3	-0.6 units on a scale Standard Deviation 13.7
Quality of Life (QoL) Change From Baseline 30 day EQ-5D	0.06 units on a scale Standard Deviation 0.18	-0.02 units on a scale Standard Deviation 0.21
Quality of Life (QoL) Change From Baseline 3 month SF-36-Physical	7.4 units on a scale Standard Deviation 10.5	5.6 units on a scale Standard Deviation 10.5
Quality of Life (QoL) Change From Baseline 3 month SF-36-Mental	4.6 units on a scale Standard Deviation 11.7	4.6 units on a scale Standard Deviation 12.6
Quality of Life (QoL) Change From Baseline 6 month KCCQ- Overall	21.9 units on a scale Standard Deviation 22.3	21.3 units on a scale Standard Deviation 22.3
Quality of Life (QoL) Change From Baseline 6 month KCCQ- Clinical	16.5 units on a scale Standard Deviation 21.5	15.9 units on a scale Standard Deviation 21.7
Quality of Life (QoL) Change From Baseline 6 month SF-36-Physical	6.3 units on a scale Standard Deviation 10.3	6.3 units on a scale Standard Deviation 10.5
Quality of Life (QoL) Change From Baseline 6 month SF-36-Mental	3.9 units on a scale Standard Deviation 11.4	3.6 units on a scale Standard Deviation 11.9
Quality of Life (QoL) Change From Baseline 6 month EQ-5D	0.04 units on a scale Standard Deviation 0.18	0.05 units on a scale Standard Deviation 0.17
Quality of Life (QoL) Change From Baseline 12 month KCCQ- Overall	20.6 units on a scale Standard Deviation 22.3	20.5 units on a scale Standard Deviation 22.2
Quality of Life (QoL) Change From Baseline 12 month KCCQ- Clinical	15.1 units on a scale Standard Deviation 21.4	14.8 units on a scale Standard Deviation 21.6
Quality of Life (QoL) Change From Baseline 12 month SF-36-Mental	4.0 units on a scale Standard Deviation 11.3	4.1 units on a scale Standard Deviation 12.0
Quality of Life (QoL) Change From Baseline 12 month EQ-5D	0.04 units on a scale Standard Deviation 0.16	0.03 units on a scale Standard Deviation 0.18
Quality of Life (QoL) Change From Baseline 18 month KCCQ- Overall	19.7 units on a scale Standard Deviation 21.5	20.2 units on a scale Standard Deviation 22.1
Quality of Life (QoL) Change From Baseline 18 month KCCQ- Clinical	14.0 units on a scale Standard Deviation 20.7	14.0 units on a scale Standard Deviation 21.9
Quality of Life (QoL) Change From Baseline 18 month SF-36-Physical	4.2 units on a scale Standard Deviation 10.4	4.3 units on a scale Standard Deviation 10.8
Quality of Life (QoL) Change From Baseline 18 month SF-36-Mental	4.3 units on a scale Standard Deviation 11.1	3.8 units on a scale Standard Deviation 11.9
Quality of Life (QoL) Change From Baseline 18 month EQ-5D	0.03 units on a scale Standard Deviation 0.17	0.03 units on a scale Standard Deviation 0.17
Quality of Life (QoL) Change From Baseline 24 month KCCQ- Overall	18.9 units on a scale Standard Deviation 21.2	18.6 units on a scale Standard Deviation 22.9
Quality of Life (QoL) Change From Baseline 24 month KCCQ- Clinical	12.7 units on a scale Standard Deviation 20.5	12.3 units on a scale Standard Deviation 22.5
Quality of Life (QoL) Change From Baseline 24 month SF-36-Physical	3.9 units on a scale Standard Deviation 9.9	4.0 units on a scale Standard Deviation 10.8
Quality of Life (QoL) Change From Baseline 24 month SF-36-Mental	3.6 units on a scale Standard Deviation 11.3	3.7 units on a scale Standard Deviation 12.2
Quality of Life (QoL) Change From Baseline 24 month EQ-5D	0.02 units on a scale Standard Deviation 0.17	0.02 units on a scale Standard Deviation 0.19

SECONDARY outcome

Timeframe: discharge, 6 months, 12 months, and 24 months. Data for 3-5 years will be posted once data is complete

Population: Participant Population= Consisted of all randomized subjects with a valve implanted

Using the following measure: -Transvalvular mean gradient

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=863 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=794 Participants Surgical Aortic Valve Replacement (SAVR)
Transvalvular Mean Gradient (in mmHg) as an Assessment of Prosthetic Valve Performance discharge	8.82 mmHg Standard Deviation 3.89	12.39 mmHg Standard Deviation 5.71
Transvalvular Mean Gradient (in mmHg) as an Assessment of Prosthetic Valve Performance 6 months	8.28 mmHg Standard Deviation 3.88	11.10 mmHg Standard Deviation 4.72
Transvalvular Mean Gradient (in mmHg) as an Assessment of Prosthetic Valve Performance 12 months	8.34 mmHg Standard Deviation 3.89	11.57 mmHg Standard Deviation 5.16
Transvalvular Mean Gradient (in mmHg) as an Assessment of Prosthetic Valve Performance 24 months	8.20 mmHg Standard Deviation 3.85	11.55 mmHg Standard Deviation 5.43

SECONDARY outcome

Timeframe: discharge, 6 months, 12 months, and 24 months. Data for 3-5 years will be posted once data is complete

Population: Participant Population= Consisted of all randomized subjects with a valve implanted

Using the following measure: -Effective Orifice Area (cm\^2)

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=863 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=794 Participants Surgical Aortic Valve Replacement (SAVR)
Effective Orifice Area as an Assessment of Prosthetic Valve Performance discharge EOA	2.13 cm^2 Standard Deviation 0.57	1.82 cm^2 Standard Deviation 0.63
Effective Orifice Area as an Assessment of Prosthetic Valve Performance 6 months EOA	2.14 cm^2 Standard Deviation 0.61	1.80 cm^2 Standard Deviation 0.57
Effective Orifice Area as an Assessment of Prosthetic Valve Performance 12 months EOA	2.13 cm^2 Standard Deviation 0.59	1.78 cm^2 Standard Deviation 0.59
Effective Orifice Area as an Assessment of Prosthetic Valve Performance 24 months EOA	2.15 cm^2 Standard Deviation 0.63	1.77 cm^2 Standard Deviation 0.55

SECONDARY outcome

Timeframe: discharge, 6 months, 12 months, and 24 months. Data for 3-5 years will be posted once data is complete

Population: Participant Population= Consisted of all randomized subjects with a valve implanted

Using the following measure: \- Degree of Aortic Valve Regurgitation (Transvalvular and Paravalvular)

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=863 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=794 Participants Surgical Aortic Valve Replacement (SAVR)
Degree of Aortic Valve Regurgitation as an Assessment of Prosthetic Valve Performance Discharge : Total Aortic Regurgitation- None	24.9 Percentage of participants	67.9 Percentage of participants
Degree of Aortic Valve Regurgitation as an Assessment of Prosthetic Valve Performance Discharge : Total Aortic Regurgitation- Trace	35.7 Percentage of participants	24.6 Percentage of participants
Degree of Aortic Valve Regurgitation as an Assessment of Prosthetic Valve Performance Discharge : Total Aortic Regurgitation- Mild	35.9 Percentage of participants	6.8 Percentage of participants
Degree of Aortic Valve Regurgitation as an Assessment of Prosthetic Valve Performance Discharge : Total Aortic Regurgitation- Moderate	3.2 Percentage of participants	0.7 Percentage of participants
Degree of Aortic Valve Regurgitation as an Assessment of Prosthetic Valve Performance Discharge : Total Aortic Regurgitation- Severe	0.2 Percentage of participants	0.0 Percentage of participants
Degree of Aortic Valve Regurgitation as an Assessment of Prosthetic Valve Performance 6 months : Total Aortic Regurgitation- None	28.4 Percentage of participants	67.0 Percentage of participants
Degree of Aortic Valve Regurgitation as an Assessment of Prosthetic Valve Performance 6 months : Total Aortic Regurgitation- Trace	32.2 Percentage of participants	24.3 Percentage of participants
Degree of Aortic Valve Regurgitation as an Assessment of Prosthetic Valve Performance 6 months : Total Aortic Regurgitation- Mild	34.7 Percentage of participants	7.8 Percentage of participants
Degree of Aortic Valve Regurgitation as an Assessment of Prosthetic Valve Performance 6 months : Total Aortic Regurgitation- Moderate	4.6 Percentage of participants	0.8 Percentage of participants
Degree of Aortic Valve Regurgitation as an Assessment of Prosthetic Valve Performance 6 months : Total Aortic Regurgitation- Severe	0.1 Percentage of participants	0.2 Percentage of participants
Degree of Aortic Valve Regurgitation as an Assessment of Prosthetic Valve Performance 12 months : Total Aortic Regurgitation- None	32.0 Percentage of participants	67.6 Percentage of participants
Degree of Aortic Valve Regurgitation as an Assessment of Prosthetic Valve Performance 12 months : Total Aortic Regurgitation- Trace	28.8 Percentage of participants	23.5 Percentage of participants
Degree of Aortic Valve Regurgitation as an Assessment of Prosthetic Valve Performance 12 months : Total Aortic Regurgitation- Mild	34.1 Percentage of participants	8.3 Percentage of participants
Degree of Aortic Valve Regurgitation as an Assessment of Prosthetic Valve Performance 12 months : Total Aortic Regurgitation- Moderate	5.1 Percentage of participants	0.7 Percentage of participants
Degree of Aortic Valve Regurgitation as an Assessment of Prosthetic Valve Performance 12 months : Total Aortic Regurgitation- Severe	0.0 Percentage of participants	0.0 Percentage of participants
Degree of Aortic Valve Regurgitation as an Assessment of Prosthetic Valve Performance 24 months : Total Aortic Regurgitation- None	35.1 Percentage of participants	67.7 Percentage of participants
Degree of Aortic Valve Regurgitation as an Assessment of Prosthetic Valve Performance 24 months : Total Aortic Regurgitation- Trace	30.5 Percentage of participants	25.3 Percentage of participants
Degree of Aortic Valve Regurgitation as an Assessment of Prosthetic Valve Performance 24 months : Total Aortic Regurgitation- Mild	30.0 Percentage of participants	6.2 Percentage of participants
Degree of Aortic Valve Regurgitation as an Assessment of Prosthetic Valve Performance 24 months : Total Aortic Regurgitation- Moderate	4.2 Percentage of participants	0.6 Percentage of participants
Degree of Aortic Valve Regurgitation as an Assessment of Prosthetic Valve Performance 24 months : Total Aortic Regurgitation- Severe	0.2 Percentage of participants	0.2 Percentage of participants

SECONDARY outcome

Timeframe: 30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete.

Population: Participant Population= Consisted of all randomized subjects with an attempted implant procedure.

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=864 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=796 Participants Surgical Aortic Valve Replacement (SAVR)
Percentage of Participants With Aortic Valve Disease Related Hospitalizations 30 days	2.8 percentage of particpants	4.1 percentage of particpants
Percentage of Participants With Aortic Valve Disease Related Hospitalizations 6 months	6.6 percentage of particpants	5.8 percentage of particpants
Percentage of Participants With Aortic Valve Disease Related Hospitalizations 12 months	8.6 percentage of particpants	7.4 percentage of particpants
Percentage of Participants With Aortic Valve Disease Related Hospitalizations 18 months	10.8 percentage of particpants	8.4 percentage of particpants
Percentage of Participants With Aortic Valve Disease Related Hospitalizations 24 months	12.8 percentage of particpants	9.5 percentage of particpants

SECONDARY outcome

Timeframe: 30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete

Population: Participant Population= Consisted of all randomized subjects with an attempted implant procedure.

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=864 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=796 Participants Surgical Aortic Valve Replacement (SAVR)
Percentage of Participants With Cardiovascular Deaths and Valve-Related Deaths 18 month cardiovascular deaths	5.9 percentage of participants	6.1 percentage of participants
Percentage of Participants With Cardiovascular Deaths and Valve-Related Deaths 18 month valve related deaths	0.0 percentage of participants	0.1 percentage of participants
Percentage of Participants With Cardiovascular Deaths and Valve-Related Deaths 24 month cardiovascular deaths	7.8 percentage of participants	7.1 percentage of participants
Percentage of Participants With Cardiovascular Deaths and Valve-Related Deaths 24 month valve related deaths	0.0 percentage of participants	0.1 percentage of participants
Percentage of Participants With Cardiovascular Deaths and Valve-Related Deaths 30 day cardiovascular deaths	2.0 percentage of participants	1.6 percentage of participants
Percentage of Participants With Cardiovascular Deaths and Valve-Related Deaths 30 day valve related deaths	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Cardiovascular Deaths and Valve-Related Deaths 6 month cardiovascular deaths	3.2 percentage of participants	3.9 percentage of participants
Percentage of Participants With Cardiovascular Deaths and Valve-Related Deaths 6 month valve related deaths	0.0 percentage of participants	0.1 percentage of participants
Percentage of Participants With Cardiovascular Deaths and Valve-Related Deaths 12 month cardiovascular deaths	4.7 percentage of participants	5.3 percentage of participants
Percentage of Participants With Cardiovascular Deaths and Valve-Related Deaths 12 month valve related deaths	0.0 percentage of participants	0.1 percentage of participants

SECONDARY outcome

Timeframe: 30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete.

Population: Participant Population= Consisted of all randomized subjects with an attempted implant procedure.

Strokes (of any severity) and Transient Ischemic Attacks (TIAs)

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=864 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=796 Participants Surgical Aortic Valve Replacement (SAVR)
Percentage of Participants With Stroke and TIAs 18 months	8.8 percentage of participants	9.4 percentage of participants
Percentage of Participants With Stroke and TIAs 30 days	4.4 percentage of participants	6.3 percentage of participants
Percentage of Participants With Stroke and TIAs 6 months	6.9 percentage of participants	7.8 percentage of participants
Percentage of Participants With Stroke and TIAs 12 months	8.0 percentage of participants	8.6 percentage of participants
Percentage of Participants With Stroke and TIAs 24 months	9.5 percentage of participants	11.2 percentage of participants

SECONDARY outcome

Timeframe: discharge or 7 days post index procedure (whichever occurred first)

Population: Participant Population= Consisted of all randomized subjects with an index procedure

Neurological injury (stroke, TIA, or encephalopathy)

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=863 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=795 Participants Surgical Aortic Valve Replacement (SAVR)
Peri-procedural Neurological Injury	4.8 percentage of participants	12.3 percentage of participants

SECONDARY outcome

Timeframe: Procedure through 30 day visit

Population: Participant Population= Consisted of all randomized subjects with an index procedure

Index procedure related MAEs were defined as events occurring during, or as a direct result of, the index procedure.

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=863 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=795 Participants Surgical Aortic Valve Replacement (SAVR)
Index Procedure Related Major Adverse Events (MAEs)	23.5 percentage of participants	30.4 percentage of participants

SECONDARY outcome

Timeframe: Number of days from admission to discharge (expected average of 7 days)

Population: Participant Population= Consisted of all randomized subjects with an index procedure

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=863 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=795 Participants Surgical Aortic Valve Replacement (SAVR)
Length of Index Procedure Hospital Stay	5.7 days Standard Deviation 4.9	9.8 days Standard Deviation 8.0

SECONDARY outcome

Timeframe: post-procedure, discharge, 30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete.

Population: Participant Population= Consisted of all randomized subjects with an attempted implant procedure.

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=864 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=796 Participants Surgical Aortic Valve Replacement (SAVR)
Presence of Atrial Fibrillation post procedure	12.8 percentage of participants	8.7 percentage of participants
Presence of Atrial Fibrillation discharge	14.0 percentage of participants	22.2 percentage of participants
Presence of Atrial Fibrillation 30 days	13.6 percentage of participants	14.4 percentage of participants
Presence of Atrial Fibrillation 6 months	14.1 percentage of participants	12.1 percentage of participants
Presence of Atrial Fibrillation 12 months	13.4 percentage of participants	11.7 percentage of participants
Presence of Atrial Fibrillation 18 months	13.6 percentage of participants	11.9 percentage of participants
Presence of Atrial Fibrillation 24 months	15.1 percentage of participants	12.2 percentage of participants

SECONDARY outcome

Timeframe: Number of days from admission to discharge (expected average of 7 days)

Population: Participant Population =Consisted of all randomized subjects with a TAVR index procedure who were evaluable for device success.

* Absence of procedural mortality * Correct positioning of a single prosthetic heart valve into the proper anatomical location * Intended performance of the prosthetic heart valve (no prosthesis-patient mismatch and mean aortic valve gradient \<20 mmHg or peak velocity \<3 m/s, AND no moderate or severe prosthetic valve regurgitation)

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=863 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR Surgical Aortic Valve Replacement (SAVR)
Device Success (Medtronic CoreValve® System Subjects Only)	77.0 percentage of participants	—

SECONDARY outcome

Timeframe: Number of days from admission to discharge (expected average of 7 days)

Population: Participant Population= Consisted of all randomized subjects with a TAVR index procedure who were evaluable for procedural success.

Defined by device success and absence of in-hospital major adverse cardiovascular and cerebrovascular events (MACCE)

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=863 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR Surgical Aortic Valve Replacement (SAVR)
Procedural Success (Medtronic CoreValve® System Subjects Only)	74.7 percentage of participants	—

SECONDARY outcome

Timeframe: 6 months, 12 months, and 24 months. Data for 3-5 years will be posted once data is complete.

Population: Participant Population= Consisted of all subjects with a valve implanted

Prosthetic Valve Dysfunction (PVD) was defined according to Valve Academic Research Consortium (VARC) II using the Core Lab Echocardiography assessments including aortic regurgitation (AR) and aortic stenosis (AS) evaluations. Total aortic regurgitation (AR) reported as moderate or severe was considered PVD defined as: * Mean aortic valve gradient ≥20 mmHg AND ((EOA ≤0.9 cm2 if BSA \<1.6 or ≤1.1 cm2 if BSA ≥1.6) OR DVI \<0. 35 m/s) OR * moderate or severe total AR

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=864 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=796 Participants Surgical Aortic Valve Replacement (SAVR)
Evidence of Prosthetic Valve Dysfunction (Medtronic CoreValve® System Subjects Only) 6 month	6.0 percentage of participants	4.1 percentage of participants
Evidence of Prosthetic Valve Dysfunction (Medtronic CoreValve® System Subjects Only) 12 month	6.7 percentage of participants	6.4 percentage of participants
Evidence of Prosthetic Valve Dysfunction (Medtronic CoreValve® System Subjects Only) 24 month	6.0 percentage of participants	5.8 percentage of participants

SECONDARY outcome

Timeframe: 30 Days

Population: Participant Population= Consisted of all randomized subjects with an attempted implant procedure.

Percentage of participants with VARC II early safety composite at 30 days

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=864 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=796 Participants Surgical Aortic Valve Replacement (SAVR)
Percentage of Participants With Early Safety Endpoint	12.5 percentage of participants	15.8 percentage of participants

SECONDARY outcome

Timeframe: 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete

Population: Participant Population= Consisted of all randomized subjects with an attempted implant procedure.

Combined clinical efficacy after 30 days was defined as the composite of all-cause mortality, all strokes (disabling and non-disabling), hospitalization for valve-related symptoms or worsening congestive heart failure, NYHA III or IV, and valve-related dysfunction.

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=864 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=796 Participants Surgical Aortic Valve Replacement (SAVR)
Percentage of Participants With Clinical Efficacy (After 30 Days) 6 months	12.8 percentage of participants	9.9 percentage of participants
Percentage of Participants With Clinical Efficacy (After 30 Days) 12 months	23.5 percentage of participants	21.0 percentage of participants
Percentage of Participants With Clinical Efficacy (After 30 Days) 18 months	26.3 percentage of participants	22.6 percentage of participants
Percentage of Participants With Clinical Efficacy (After 30 Days) 24 months	33.9 percentage of participants	33.0 percentage of participants

SECONDARY outcome

Timeframe: 30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is available.

Population: Participant Population= Consisted of all randomized subjects with an attempted implant procedure.

The VARC II time-related valve safety composite was defined as the rate of valve-related dysfunction (mean aortic valve gradient ≥ 20 mm Hg, EOA ≤ 0.9-1.1 cm2 depending on body surface area and/or DVI \<0.35, AND/ OR moderate or severe prosthetic valve regurgitation), aortic valve reintervention, prosthetic valve endocarditis, prosthetic valve thrombosis, thromboembolic events, and VARC II bleeding events.

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=864 Participants Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=796 Participants Surgical Aortic Valve Replacement (SAVR)
Percentage of Participants With Time-Related Safety 30 days	28.8 percentage of participants	61.7 percentage of participants
Percentage of Participants With Time-Related Safety 6 months	38.5 percentage of participants	69.6 percentage of participants
Percentage of Participants With Time-Related Safety 12 months	45.1 percentage of participants	72.1 percentage of participants
Percentage of Participants With Time-Related Safety 18 months	42.1 percentage of participants	67.8 percentage of participants
Percentage of Participants With Time-Related Safety 24 months	53.0 percentage of participants	77.3 percentage of participants

SECONDARY outcome

Timeframe: Procedure

Population: Participant Population= Consisted of all subjects in whom the resheath or recapture feature of the Evolut R system was attempted

The Evolut™ R system provides operators with the ability to resheath or recapture the valve before it is completely deployed in the event of initial suboptimal positioning. Successful resheath was defined as successfully retrieving a portion of the valve into the capsule of the delivery catheter, and successful recapture was defined as successfully recapturing the entirety of the valve into the capsule of the delivery catheter.

Outcome measures

Outcome measures
Measure	Medtronic CoreValve® System TAVI n=53 attempts Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR Surgical Aortic Valve Replacement (SAVR)
Resheath and Recapture Success (Evolut R Only) Resheath	100 percentage of attempts	—
Resheath and Recapture Success (Evolut R Only) Recapture	89.7 percentage of attempts	—
Resheath and Recapture Success (Evolut R Only) Resheath or Recapture	92.5 percentage of attempts	—

Adverse Events

Medtronic CoreValve® System TAVI

Serious events: 718 serious events

Other events: 803 other events

Deaths: 98 deaths

SAVR

Serious events: 694 serious events

Other events: 754 other events

Deaths: 80 deaths

Serious adverse events

Other adverse events

Additional Information

Peggy Yunker

Medtronic, Inc.

Phone: 763-514-4000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Medtronic CoreValve® System TAVI n=864 participants at risk Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	SAVR n=796 participants at risk Surgical Aortic Valve Replacement (SAVR)
Blood and lymphatic system disorders ANAEMIA	9.3% 80/864 • Number of events 84 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	12.4% 99/796 • Number of events 100 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.
Blood and lymphatic system disorders LEUKOCYTOSIS	8.1% 70/864 • Number of events 71 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	18.3% 146/796 • Number of events 154 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.
Blood and lymphatic system disorders THROMBOCYTOPENIA	15.4% 133/864 • Number of events 140 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	23.6% 188/796 • Number of events 198 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.
Cardiac disorders ATRIAL FIBRILLATION	13.0% 112/864 • Number of events 120 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	28.9% 230/796 • Number of events 239 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.
Cardiac disorders ATRIOVENTRICULAR BLOCK FIRST DEGREE	9.3% 80/864 • Number of events 82 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	8.4% 67/796 • Number of events 68 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.
Cardiac disorders BUNDLE BRANCH BLOCK LEFT	29.9% 258/864 • Number of events 265 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	6.9% 55/796 • Number of events 59 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.
Gastrointestinal disorders CONSTIPATION	0.00% 0/864 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	6.7% 53/796 • Number of events 56 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.
Gastrointestinal disorders NAUSEA	0.00% 0/864 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	5.3% 42/796 • Number of events 43 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.
General disorders OEDEMA PERIPHERAL	5.2% 45/864 • Number of events 48 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	5.9% 47/796 • Number of events 49 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.
Infections and infestations URINARY TRACT INFECTION	7.5% 65/864 • Number of events 77 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	11.1% 88/796 • Number of events 102 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.
Metabolism and nutrition disorders FLUID OVERLOAD	0.00% 0/864 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	15.3% 122/796 • Number of events 127 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.
Metabolism and nutrition disorders HYPERGLYCAEMIA	6.1% 53/864 • Number of events 54 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	12.8% 102/796 • Number of events 102 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.
Metabolism and nutrition disorders HYPERKALAEMIA	0.00% 0/864 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	5.2% 41/796 • Number of events 42 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.
Metabolism and nutrition disorders HYPOKALAEMIA	5.3% 46/864 • Number of events 49 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	6.7% 53/796 • Number of events 55 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.
Metabolism and nutrition disorders HYPONATRAEMIA	0.00% 0/864 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	6.5% 52/796 • Number of events 56 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.
Psychiatric disorders CONFUSIONAL STATE	0.00% 0/864 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	5.5% 44/796 • Number of events 47 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.
Renal and urinary disorders ACUTE KIDNEY INJURY	9.1% 79/864 • Number of events 91 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	15.7% 125/796 • Number of events 138 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.
Respiratory, thoracic and mediastinal disorders ATELECTASIS	7.2% 62/864 • Number of events 64 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	19.0% 151/796 • Number of events 154 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	5.6% 48/864 • Number of events 50 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	0.00% 0/796 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	8.1% 70/864 • Number of events 76 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	27.1% 216/796 • Number of events 223 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.
Vascular disorders HAEMATOMA	5.4% 47/864 • Number of events 49 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	0.00% 0/796 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.
Vascular disorders HYPERTENSION	14.2% 123/864 • Number of events 139 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	12.6% 100/796 • Number of events 107 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.
Vascular disorders HYPOTENSION	5.4% 47/864 • Number of events 50 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.	10.3% 82/796 • Number of events 83 • Adverse events (AEs) were collected from study enrollment through the 24 month follow-up visit. Adverse event data are currently available and reported for up to 24 months. All new or worsening AEs were collected through 24 months.