Trial Outcomes & Findings for Efficacy and Safety Study of Apixaban for Extended Treatment of Deep Vein Thrombosis or Pulmonary Embolism (NCT NCT00633893)

NCT ID: NCT00633893

Last Updated: 2013-11-25

Results Overview

VTE included: nonfatal deep vein thrombosis (DVT) or nonfatal pulmonary embolism (PE). All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. For missing endpoint data, participants were imputed as having had a primary efficacy outcome event.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 2711 participants
• Primary outcome timeframe: Day 1 up to 12 Months
• Results posted on: 2013-11-25

Participant Flow

First participant, first visit: 16 May 2008; Last participant, last visit: 24 August 2012.

2711 enrolled/2482 randomized: 133 did not meet inclusion, exclusion criteria; 48 withdrew consent; 8 non-compliance; 3 each administrative and clinical reasons; 2 lost to follow up; 1 death; 1 adverse event (AE), 30 other. Data from 4 participants in site 0650 not analyzed/included in randomized population because source for data not confirmed.

Participant milestones

Measure	Apixaban 2.5 mg Participants received 2.5 mg oral tablet apixaban twice a day (BID)	Apixaban 5 mg Participants received 5 mg oral tablet apixaban BID.	Placebo Participants received matching placebo oral tablet BID.
Overall Study STARTED	840	813	829
Overall Study COMPLETED	726	684	641
Overall Study NOT COMPLETED	114	129	188

Reasons for withdrawal

Measure	Apixaban 2.5 mg Participants received 2.5 mg oral tablet apixaban twice a day (BID)	Apixaban 5 mg Participants received 5 mg oral tablet apixaban BID.	Placebo Participants received matching placebo oral tablet BID.
Overall Study Death	1	3	9
Overall Study Adverse Event	65	58	126
Overall Study Withdrawal by Subject	7	12	6
Overall Study Lost to Follow-up	2	4	8
Overall Study Poor/non-compliance	5	12	3
Overall Study Pregnancy	2	1	1
Overall Study Not meet/no longer meets criteria	4	6	4
Overall Study Other	28	33	31

Baseline Characteristics

Efficacy and Safety Study of Apixaban for Extended Treatment of Deep Vein Thrombosis or Pulmonary Embolism

Baseline characteristics by cohort

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=813 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=829 Participants Participants received matching placebo oral tablet BID.	Total n=2482 Participants Total of all reporting groups
Age Continuous	56.6 years STANDARD_DEVIATION 15.3 • n=5 Participants	56.4 years STANDARD_DEVIATION 15.6 • n=7 Participants	57.1 years STANDARD_DEVIATION 15.2 • n=5 Participants	56.7 years STANDARD_DEVIATION 15.4 • n=4 Participants
Sex: Female, Male Female	353 Participants n=5 Participants	344 Participants n=7 Participants	361 Participants n=5 Participants	1058 Participants n=4 Participants
Sex: Female, Male Male	487 Participants n=5 Participants	469 Participants n=7 Participants	468 Participants n=5 Participants	1424 Participants n=4 Participants
Region of Enrollment Portugal	1 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants
Region of Enrollment United States	88 participants n=5 Participants	75 participants n=7 Participants	96 participants n=5 Participants	259 participants n=4 Participants
Region of Enrollment Philippines	5 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	11 participants n=4 Participants
Region of Enrollment Hong Kong	4 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants	11 participants n=4 Participants
Region of Enrollment Spain	27 participants n=5 Participants	25 participants n=7 Participants	26 participants n=5 Participants	78 participants n=4 Participants
Region of Enrollment Ukraine	87 participants n=5 Participants	77 participants n=7 Participants	88 participants n=5 Participants	252 participants n=4 Participants
Region of Enrollment Chile	2 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	5 participants n=4 Participants
Region of Enrollment Russian Federation	45 participants n=5 Participants	49 participants n=7 Participants	46 participants n=5 Participants	140 participants n=4 Participants
Region of Enrollment Israel	34 participants n=5 Participants	34 participants n=7 Participants	34 participants n=5 Participants	102 participants n=4 Participants
Region of Enrollment Italy	67 participants n=5 Participants	65 participants n=7 Participants	61 participants n=5 Participants	193 participants n=4 Participants
Region of Enrollment India	24 participants n=5 Participants	23 participants n=7 Participants	24 participants n=5 Participants	71 participants n=4 Participants
Region of Enrollment France	60 participants n=5 Participants	55 participants n=7 Participants	50 participants n=5 Participants	165 participants n=4 Participants
Region of Enrollment Australia	30 participants n=5 Participants	28 participants n=7 Participants	31 participants n=5 Participants	89 participants n=4 Participants
Region of Enrollment Denmark	47 participants n=5 Participants	58 participants n=7 Participants	42 participants n=5 Participants	147 participants n=4 Participants
Region of Enrollment South Africa	34 participants n=5 Participants	42 participants n=7 Participants	30 participants n=5 Participants	106 participants n=4 Participants
Region of Enrollment Korea, Republic of	4 participants n=5 Participants	3 participants n=7 Participants	2 participants n=5 Participants	9 participants n=4 Participants
Region of Enrollment Austria	12 participants n=5 Participants	8 participants n=7 Participants	11 participants n=5 Participants	31 participants n=4 Participants
Region of Enrollment United Kingdom	33 participants n=5 Participants	29 participants n=7 Participants	30 participants n=5 Participants	92 participants n=4 Participants
Region of Enrollment Czech Republic	43 participants n=5 Participants	49 participants n=7 Participants	48 participants n=5 Participants	140 participants n=4 Participants
Region of Enrollment Mexico	22 participants n=5 Participants	18 participants n=7 Participants	22 participants n=5 Participants	62 participants n=4 Participants
Region of Enrollment Canada	22 participants n=5 Participants	17 participants n=7 Participants	15 participants n=5 Participants	54 participants n=4 Participants
Region of Enrollment Argentina	7 participants n=5 Participants	9 participants n=7 Participants	6 participants n=5 Participants	22 participants n=4 Participants
Region of Enrollment Poland	45 participants n=5 Participants	44 participants n=7 Participants	48 participants n=5 Participants	137 participants n=4 Participants
Region of Enrollment Brazil	19 participants n=5 Participants	24 participants n=7 Participants	30 participants n=5 Participants	73 participants n=4 Participants
Region of Enrollment Singapore	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants	6 participants n=4 Participants
Region of Enrollment Romania	6 participants n=5 Participants	7 participants n=7 Participants	7 participants n=5 Participants	20 participants n=4 Participants
Region of Enrollment Norway	9 participants n=5 Participants	9 participants n=7 Participants	10 participants n=5 Participants	28 participants n=4 Participants
Region of Enrollment Germany	62 participants n=5 Participants	55 participants n=7 Participants	60 participants n=5 Participants	177 participants n=4 Participants
Index Event Classification Proximal DVT	544 participants n=5 Participants	527 participants n=7 Participants	551 participants n=5 Participants	1622 participants n=4 Participants
Index Event Classification PE	296 participants n=5 Participants	286 participants n=7 Participants	278 participants n=5 Participants	860 participants n=4 Participants

PRIMARY outcome

Timeframe: Day 1 up to 12 Months

Population: Intent to treat: all randomized participants with consent. Analyzed per randomized treatment assigned. (n) number of events=32, 34, 96 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively; number of events imputed=13, 20, 19, respectively. Confidence interval (CI) for event rate was calculated based on the Wald asymptotic confidence limits.

VTE included: nonfatal deep vein thrombosis (DVT) or nonfatal pulmonary embolism (PE). All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. For missing endpoint data, participants were imputed as having had a primary efficacy outcome event.

Outcome measures

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=813 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=829 Participants Participants received matching placebo oral tablet BID.
Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or All-Cause Death During the Intended Treatment Period - Randomized Population With Imputation	0.0381 Proportion of participants Interval 0.0252 to 0.051	0.0418 Proportion of participants Interval 0.0281 to 0.0556	0.1158 Proportion of participants Interval 0.094 to 0.1376

PRIMARY outcome

Timeframe: Day 1 up to 12 months

Population: Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned.(n)number of events = 19, 14, 77 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. All events were counted; no events were imputed.

VTE included: nonfatal DVT or nonfatal PE. Event rate (proportion of participants with event) calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for these endpoints; participants who had an event during the intended treatment period were counted. Confidence interval (CI) for single event rate was calculated based on the Wald asymptotic confidence limits.

Outcome measures

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=813 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=829 Participants Participants received matching placebo oral tablet BID.
Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or All-Cause Death During the Intended Treatment Period - Randomized Population Without Imputation	0.0226 Proportion of participants Interval 0.0126 to 0.0327	0.0172 Proportion of participants Interval 0.0083 to 0.0262	0.0929 Proportion of participants Interval 0.0731 to 0.1126

SECONDARY outcome

Timeframe: Day 1 up to 12 Months

Population: ITT: all randomized participants with consent. Analyzed per randomized treatment assigned. (n) number of events=27, 34, 92 in apixaban 2.5 mg, 5 mg, placebo arms, respectively. Number of imputed events=13, 20, 19 in apixaban 2.5 mg, 5 mg, placebo arms, respectively. CI for single event rate was calculated based on Wald asymptotic confidence limits.

VTE includes nonfatal DVT or nonfatal PE. All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. For missing endpoint data, participants were imputed as having had a primary efficacy outcome event.

Outcome measures

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=813 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=829 Participants Participants received matching placebo oral tablet BID.
Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or VTE-related Death During the Intended Treatment Period - Randomized Population With Imputation	0.0321 Proportion of participants Interval 0.0202 to 0.0441	0.0418 Proportion of participants Interval 0.0281 to 0.0556	0.1110 Proportion of participants Interval 0.0896 to 0.1324

SECONDARY outcome

Timeframe: Day 1 up to 12 Months

Population: Intent to treat: all randomized participants with consent.(n)number of events=27, 34, 95 in apixaban 2.5 mg, 5 mg, placebo arms, respectively. The (n)number of imputed events were = 13, 20, 19 in apixaban 2.5 mg, 5 mg, placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits

VTE includes nonfatal DVT or nonfatal PE. All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Composite endpoint included events that occurred any time from randomization until end of the intended treatment period, regardless of whether the participants were receiving drug treatment. Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. If there were missing endpoint data, participants were imputed as having had an efficacy outcome event.

Outcome measures

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=813 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=829 Participants Participants received matching placebo oral tablet BID.
Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Cardio Vascular (CV) -Related Death During the Intended Treatment Period - Randomized Population With Imputation	0.0321 proportion of participants Interval 0.0202 to 0.0441	0.0418 proportion of participants Interval 0.0281 to 0.0556	0.1146 proportion of participants Interval 0.0929 to 0.1363

SECONDARY outcome

Timeframe: Day 1 up to 12 Months

Population: Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned. (n) number of events = 19, 28, 72 in apixaban 2.5 mg, 5 mg, placebo arms, respectively.

DVT was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and assessed by compression ultrasound and/or venography. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. Participants with missing endpoint information were classified as having had the efficacy event (imputation). Confidence interval (CI) for single event rate was calculated based on the Wald asymptotic confidence limits.

Outcome measures

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=813 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=829 Participants Participants received matching placebo oral tablet BID.
Adjudicated Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period - Randomized Population With Imputation	0.0226 Proportion of participants Interval 0.0126 to 0.0327	0.0344 Proportion of participants Interval 0.0219 to 0.047	0.0869 Proportion of participants Interval 0.0677 to 0.106

SECONDARY outcome

Timeframe: Day 1 up to 12 Months

Population: Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned. (n) number of events = 23, 25, 37 in apixaban 2.5 mg, 5 mg, placebo arms, respectively.

PE was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and was assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. Participants with missing endpoint information were classified as having had the efficacy event (imputation). CI for single event rate was calculated based on the Wald asymptotic confidence limits.

Outcome measures

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=813 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=829 Participants Participants received matching placebo oral tablet BID.
Adjudicated Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period - Randomized Population With Imputation	0.0274 Proportion of participants Interval 0.0163 to 0.0384	0.0308 Proportion of participants Interval 0.0189 to 0.0426	0.0446 Proportion of participants Interval 0.0306 to 0.0587

SECONDARY outcome

Timeframe: Day 1 up to 12 Months

Population: Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned. (n) number of events = 17, 24, 26 in apixaban 2.5 mg, 5 mg, placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.

VTE-related death defined as: PE (based on objective diagnostic testing, autopsy), unexplained death (and VTE cannot be ruled out), sudden death (and VTE cannot be ruled out). DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, death, venous/arterial thromboembolic events, bleeding, thrombocytopenia, acute myocardial infarction and stroke were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Participants with missing endpoint information were classified as having had the efficacy event (imputation).

Outcome measures

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=813 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=829 Participants Participants received matching placebo oral tablet BID.
Adjudicated Venous Thromboembolism (VTE) - Related Death During the Intended Treatment Period - Randomized Population With Imputation	0.0202 Proportion of participants Interval 0.0107 to 0.0298	0.0295 Proportion of participants Interval 0.0179 to 0.0412	0.0314 Proportion of participants Interval 0.0195 to 0.0432

SECONDARY outcome

Timeframe: Day 1 up to 12 Months

Population: Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned. number of events (n)= 17, 24, 29 in the apixaban 2.5 mg, 5 mg, placebo arms, respectively.

CV-related death was defined as myocardial infarction, stroke, or other specified cardiovascular event and were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. Participants with missing endpoint information were classified as having had the efficacy event (imputation). CI for single event rate was calculated based on the Wald asymptotic confidence limits.

Outcome measures

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=813 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=829 Participants Participants received matching placebo oral tablet BID.
Adjudicated Cardiovascular (CV)-Related Death During the Intended Treatment Period - Randomized Population With Imputation	0.0202 Proportion of Participants Interval 0.0107 to 0.0298	0.0295 Proportion of Participants Interval 0.0179 to 0.0412	0.0350 Proportion of Participants Interval 0.0225 to 0.0475

SECONDARY outcome

Timeframe: Day 1 up to 12 Months

Population: Intent to treat: all randomized participants with valid consent. (n) number of events = 22, 25, 33 in apixaban 2.5 mg, apixaban 5 mg, and placebo arms, respectively.

DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, death, venous/arterial thromboembolic events, bleeding, thrombocytopenia, acute myocardial infarction and stroke were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Participants with missing endpoint information were classified as having had the efficacy event (imputation). CI for single event rate was calculated based on the Wald asymptotic confidence limits.

Outcome measures

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=813 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=829 Participants Participants received matching placebo oral tablet BID.
Adjudicated All-Cause Death During the Intended Treatment Period - Randomized Population With Imputation	0.0262 Proportion of participants Interval 0.0154 to 0.037	0.0308 Proportion of participants Interval 0.0189 to 0.0426	0.0398 Proportion of participants Interval 0.0265 to 0.0531

SECONDARY outcome

Timeframe: Day 1 up to 12 Months

Population: Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned. In first event (first primary event) each participant counted once. In event category, each participant was counted only once in each event category but could have been counted in multiple categories.

All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. First event category was the first primary event for each participant and each participant was counted once. CV-related death was presented excluding VTE-related death. In participants with event category, each participant was counted once in each event category but could have been counted in multiple categories. No imputation was done for these endpoints; participants who had an event during the intended treatment period were counted.

Outcome measures

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=813 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=829 Participants Participants received matching placebo oral tablet BID.
Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation First event: Participants with nonfatal DVT	6 participants	7 participants	53 participants
Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation First event: Participants with nonfatal PE	7 participants	4 participants	13 participants
Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation First event: All-Cause Death	6 participants	3 participants	11 participants
Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation CV-related Death (included in all-cause total)	0 participants	0 participants	3 participants
Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation VTE-related Death (included in all-cause total)	2 participants	3 participants	7 participants
Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation Participants with event: nonfatal DVT	6 participants	8 participants	53 participants
Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation Participants with event: nonfatal PE	8 participants	4 participants	15 participants
Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation Participants with event: All cause death	7 participants	4 participants	14 participants

SECONDARY outcome

Timeframe: Day 1 up to 12 Months

Population: Treated population includes randomized participants who received at least one dose of study drug. (n) number of events = 2, 1, 4 in apixaban 2.5 mg, and 5 mg, and placebo arms, respectively.

Major bleeding was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and was defined as acute clinically overt bleeding: associated with a fall in hemoglobin of 2 grams per deciliter (g/dL) or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 milliliters (mL) or more of whole blood, or in a critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal, or another critical organ; or is fatal. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Confidence interval (CI) for event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug.

Outcome measures

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=811 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=826 Participants Participants received matching placebo oral tablet BID.
Adjudicated Major Bleeding During the Treatment Period - Treated Population	0.0024 Proportion of participants Interval 0.0 to 0.0057	0.0012 Proportion of participants Interval 0.0 to 0.0036	0.0048 Proportion of participants Interval 0.0001 to 0.0096

SECONDARY outcome

Timeframe: Day 1 up to 12 Months

Population: Treated participants were those who received at least 1 dose of study drug. (n)number of events = 27, 35, 22 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively.

Major bleeding and clinically relevant non-major bleeding were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Major bleeding was defined as acute clinically overt bleeding: associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 mL or more of whole blood, or in a critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal, or another critical organ or is fatal. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). CI for single event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug.

Outcome measures

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=811 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=826 Participants Participants received matching placebo oral tablet BID.
Adjudicated Composite of Major/Clinically Relevant Non-major Bleeding During the Treatment Period - Treated Participants	0.0321 proportion of participants Interval 0.0202 to 0.0441	0.0432 proportion of participants Interval 0.0292 to 0.0571	0.0266 proportion of participants Interval 0.0157 to 0.0376

SECONDARY outcome

Timeframe: Day 1 up to 12 months

Population: Treated population includes randomized participants who received at least one dose of study drug. (n)number of events = 25, 34, 19 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively.

Non-major clinically relevant bleeding was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and defined as: acute clinically overt bleeding compromising hemodynamics; leading to hospitalization; traumatic subcutaneous hematoma; intramuscular hematoma; epistaxis that lasted for more than 5 minutes, was repetitive or led to an intervention; spontaneous gingival bleeding (or lasting more than 5 minutes); spontaneous hematuria (macroscopic or lasted more than 24 hours after instrumentation of the urogenital tract); macroscopic gastrointestinal hemorrhage (including at least 1 episode of melena or hematemesis (if clinically apparent with positive results on a fecal occult-blood test); rectal blood loss. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). CI for single event rate was calculated based on the Wald asymptotic confidence limits.

Outcome measures

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=811 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=826 Participants Participants received matching placebo oral tablet BID.
Adjudicated Clinically Relevant Non-major Bleeding During the Treatment Period - Treated Participants	0.0298 Proportion of participants Interval 0.0183 to 0.0413	0.0419 Proportion of participants Interval 0.0281 to 0.0557	0.0230 Proportion of participants Interval 0.0128 to 0.0332

SECONDARY outcome

Timeframe: Day 1 up to 12 months

Population: Treated population includes randomized participants who received at least one dose of study drug. (n)number of events = 75, 98, 58 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively.

All bleeding events were reviewed by the central independent adjudication committee blinded to treatment and classified as major bleeding, clinically relevant non-major bleeding, minor bleeding or no bleeding. If event was not major or clinically relevant non-major, it was judged to be minor. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Confidence interval (CI) for single event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug.

Outcome measures

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=811 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=826 Participants Participants received matching placebo oral tablet BID.
Adjudicated Clinically Relevant Minor Bleeding During the Treatment Period - Treated Participants	0.0893 Proportion of participants Interval 0.07 to 0.1086	0.1208 Proportion of participants Interval 0.0984 to 0.1433	0.0702 Proportion of participants Interval 0.0528 to 0.0876

SECONDARY outcome

Timeframe: Day 1 up to 12 months

Population: Treated population includes randomized participants who received at least one dose of study drug. (n) number of events = 94, 121, 74 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively.

All bleeding events were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Total bleeding was defined as any major, clinically relevant non-major, or minor bleeding. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). CI for single event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug.

Outcome measures

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=811 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=826 Participants Participants received matching placebo oral tablet BID.
Adjudicated Total Bleeding During the Treatment Period - Treated Participants	0.1119 Proportion of participants Interval 0.0906 to 0.1332	0.1492 Proportion of participants Interval 0.1247 to 0.1737	0.0896 Proportion of participants Interval 0.0701 to 0.1091

SECONDARY outcome

Timeframe: Day 1 up to 12 Months

Population: Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 14, 14, 73 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.

VTE related death defined as PE (based on objective diagnostic testing, autopsy), unexplained death (and VTE cannot be ruled out), sudden death (and VTE cannot be ruled out). DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE and death, were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for these endpoints.

Outcome measures

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=813 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=829 Participants Participants received matching placebo oral tablet BID.
Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Venous Thromboembolism-related Death During the Intended Treatment Period - Randomized Population Without Imputation	0.0167 proportion of participants Interval 0.008 to 0.0253	0.0172 proportion of participants Interval 0.0083 to 0.0262	0.0881 proportion of participants Interval 0.0688 to 0.1073

SECONDARY outcome

Timeframe: Day 1 up to 12 Months

Population: Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 14, 14, 76 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.

CV-related death was defined as myocardial infarction, stroke, or other specified cardiovascular event. Index events of DVT and/or PE, along with myocardial infarction and stroke were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for these endpoints; participants who had an event during the intended treatment period were counted.

Outcome measures

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=813 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=829 Participants Participants received matching placebo oral tablet BID.
Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Cardio Vascular (CV) - Related Death During the Intended Treatment Period - Randomized Population Without Imputation	0.0167 proportion of participants Interval 0.008 to 0.0253	0.0172 proportion of participants Interval 0.0083 to 0.0262	0.0917 proportion of participants Interval 0.072 to 0.1113

SECONDARY outcome

Timeframe: Day 1 up to 12 Months

Population: Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 6, 8, 53 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.

DVT was adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted.

Outcome measures

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=813 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=829 Participants Participants received matching placebo oral tablet BID.
Adjudicated Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period - Randomized Population Without Imputation	0.0071 proportion of participants Interval 0.0014 to 0.0128	0.0098 proportion of participants Interval 0.0031 to 0.0166	0.0639 proportion of participants Interval 0.0473 to 0.0806

SECONDARY outcome

Timeframe: Day 1 up to 12 Months

Population: Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 8, 4, 15 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.

PE was adjudicated/confirmed by a central independent adjudication committee blinded to treatment: PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted.

Outcome measures

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=813 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=829 Participants Participants received matching placebo oral tablet BID.
Adjudicated Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period - Randomized Population Without Imputation	0.0095 Proportion of participants Interval 0.003 to 0.0161	0.0049 Proportion of participants Interval 0.0001 to 0.0097	0.0181 Proportion of participants Interval 0.009 to 0.0272

SECONDARY outcome

Timeframe: Day 1 up to 12 Months

Population: Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 2, 3, 7 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.

VTE related death defined as PE (based on objective diagnostic testing, autopsy), unexplained death (and VTE cannot be ruled out), sudden death (and VTE cannot be ruled out). DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, and death, were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint.

Outcome measures

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=813 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=829 Participants Participants received matching placebo oral tablet BID.
Adjudicated Venous Thromboembolism (VTE)- Related Death During the Intended Treatment Period - Randomized Population Without Imputation	0.0024 Proportion of participants Interval 0.0 to 0.0057	0.0037 Proportion of participants Interval 0.0 to 0.0079	0.0084 Proportion of participants Interval 0.0022 to 0.0147

SECONDARY outcome

Timeframe: Day 1 up to 12 Months

Population: Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 2, 3, 10 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.

CV-related death was defined as myocardial infarction, stroke, or other specified cardiovascular event and these were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted.

Outcome measures

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=813 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=829 Participants Participants received matching placebo oral tablet BID.
Adjudicated Cardio Vascular (CV)-Related Death During the Intended Treatment Period - Randomized Population Without Imputation	0.0024 Proportion of participants Interval 0.0 to 0.0057	0.0037 Proportion of participants Interval 0.0 to 0.0079	0.0121 Proportion of participants Interval 0.0046 to 0.0195

SECONDARY outcome

Timeframe: Day 1 up to 12 Months

Population: Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 7, 4, 14 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.

DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, death, venous/arterial thromboembolic events, bleeding, thrombocytopenia, acute myocardial infarction and stroke were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted.

Outcome measures

Measure	Apixaban 2.5 mg n=840 Participants Participants received 2.5 mg oral tablet apixaban BID.	Apixaban 5 mg n=813 Participants Participants received 5 mg oral tablet apixaban BID.	Placebo n=829 Participants Participants received matching placebo oral tablet BID.
Adjudicated All-Cause Death During the Intended Treatment Period - Randomized Population Without Imputation	0.0083 Proportion of participants Interval 0.0022 to 0.0145	0.0049 Proportion of participants Interval 0.0001 to 0.0097	0.0169 Proportion of participants Interval 0.0081 to 0.0257

Adverse Events

Apixaban 2.5mg

Serious events: 112 serious events

Other events: 341 other events

Deaths: 0 deaths

Apixaban 5mg

Serious events: 107 serious events

Other events: 305 other events

Deaths: 0 deaths

Placebo

Serious events: 158 serious events

Other events: 318 other events

Deaths: 0 deaths

Serious adverse events

Measure	Apixaban 2.5mg n=840 participants at risk Participants received 2.5 mg oral tablet apixaban BID	Apixaban 5mg n=811 participants at risk Participants received 5 mg oral tablet apixaban BID	Placebo n=826 participants at risk Participants received oral tablet of placebo BID
Blood and lymphatic system disorders ANAEMIA	0.00% 0/840 • Day 1 up to 12 months	0.37% 3/811 • Day 1 up to 12 months	0.24% 2/826 • Day 1 up to 12 months
Blood and lymphatic system disorders IRON DEFICIENCY ANAEMIA	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Cardiac disorders ACUTE CORONARY SYNDROME	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Cardiac disorders ACUTE MYOCARDIAL INFARCTION	0.12% 1/840 • Day 1 up to 12 months	0.25% 2/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Cardiac disorders ANGINA PECTORIS	0.36% 3/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Cardiac disorders ANGINA UNSTABLE	0.12% 1/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Cardiac disorders ARTERIOSCLEROSIS CORONARY ARTERY	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Cardiac disorders ATRIAL FIBRILLATION	0.24% 2/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.48% 4/826 • Day 1 up to 12 months
Cardiac disorders BRADYCARDIA	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Cardiac disorders CARDIAC ARREST	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Cardiac disorders CARDIAC FAILURE	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Cardiac disorders CARDIAC FAILURE CONGESTIVE	0.24% 2/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Cardiac disorders CARDIO-RESPIRATORY ARREST	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Cardiac disorders CONGESTIVE CARDIOMYOPATHY	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Cardiac disorders CORONARY ARTERY DISEASE	0.24% 2/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Cardiac disorders EXTRASYSTOLES	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Cardiac disorders MITRAL VALVE INCOMPETENCE	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Cardiac disorders MYOCARDIAL INFARCTION	0.12% 1/840 • Day 1 up to 12 months	0.37% 3/811 • Day 1 up to 12 months	0.24% 2/826 • Day 1 up to 12 months
Cardiac disorders MYOCARDIAL ISCHAEMIA	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.36% 3/826 • Day 1 up to 12 months
Cardiac disorders SICK SINUS SYNDROME	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Cardiac disorders TACHYCARDIA	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Cardiac disorders VENTRICULAR FIBRILLATION	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Congenital, familial and genetic disorders HIP DYSPLASIA	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Ear and labyrinth disorders OTOSCLEROSIS	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Ear and labyrinth disorders VERTIGO	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.24% 2/826 • Day 1 up to 12 months
Endocrine disorders THYROIDITIS	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Eye disorders CATARACT	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Eye disorders EYE HAEMORRHAGE	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.24% 2/826 • Day 1 up to 12 months
Eye disorders MACULAR OEDEMA	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Eye disorders RETINAL HAEMORRHAGE	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Eye disorders RETINAL VEIN OCCLUSION	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Eye disorders RETINAL VEIN THROMBOSIS	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Gastrointestinal disorders ABDOMINAL PAIN	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Gastrointestinal disorders ABDOMINAL PAIN LOWER	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Gastrointestinal disorders ABDOMINAL STRANGULATED HERNIA	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Gastrointestinal disorders ANAL FISSURE	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Gastrointestinal disorders GASTRIC ULCER HAEMORRHAGE	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Gastrointestinal disorders GASTRITIS	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Gastrointestinal disorders GASTROINTESTINAL HAEMORRHAGE	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Gastrointestinal disorders GASTROOESOPHAGEAL REFLUX DISEASE	0.24% 2/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Gastrointestinal disorders HAEMATEMESIS	0.24% 2/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Gastrointestinal disorders HAEMORRHOIDAL HAEMORRHAGE	0.00% 0/840 • Day 1 up to 12 months	0.25% 2/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Gastrointestinal disorders HIATUS HERNIA	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Gastrointestinal disorders ILEUS	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Gastrointestinal disorders INGUINAL HERNIA	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Gastrointestinal disorders INTESTINAL ISCHAEMIA	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Gastrointestinal disorders PANCREATITIS	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Gastrointestinal disorders PANCREATITIS ACUTE	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Gastrointestinal disorders POLYP COLORECTAL	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Gastrointestinal disorders RECTAL HAEMORRHAGE	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Gastrointestinal disorders SMALL INTESTINAL OBSTRUCTION	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Gastrointestinal disorders UPPER GASTROINTESTINAL HAEMORRHAGE	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Gastrointestinal disorders VOMITING	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
General disorders ASTHENIA	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
General disorders CHEST PAIN	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
General disorders DEATH	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.24% 2/826 • Day 1 up to 12 months
General disorders FATIGUE	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
General disorders GENERAL PHYSICAL HEALTH DETERIORATION	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
General disorders MULTI-ORGAN FAILURE	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
General disorders NON-CARDIAC CHEST PAIN	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.24% 2/826 • Day 1 up to 12 months
General disorders OEDEMA PERIPHERAL	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
General disorders PYREXIA	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
General disorders SUDDEN DEATH	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.36% 3/826 • Day 1 up to 12 months
Hepatobiliary disorders BILE DUCT STONE	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Hepatobiliary disorders CHOLANGITIS ACUTE	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Hepatobiliary disorders CHOLECYSTITIS	0.00% 0/840 • Day 1 up to 12 months	0.25% 2/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Hepatobiliary disorders CHOLECYSTITIS ACUTE	0.36% 3/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Hepatobiliary disorders CHOLECYSTITIS CHRONIC	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Hepatobiliary disorders CHOLELITHIASIS	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Hepatobiliary disorders DRUG-INDUCED LIVER INJURY	0.00% 0/840 • Day 1 up to 12 months	0.25% 2/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Hepatobiliary disorders HEPATITIS	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Immune system disorders AMYLOIDOSIS	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Immune system disorders ANTIPHOSPHOLIPID SYNDROME	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Infections and infestations ACUTE SINUSITIS	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Infections and infestations BRONCHITIS	0.12% 1/840 • Day 1 up to 12 months	0.25% 2/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Infections and infestations BRONCHOPNEUMONIA	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Infections and infestations CELLULITIS	0.24% 2/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.24% 2/826 • Day 1 up to 12 months
Infections and infestations DIVERTICULITIS	0.12% 1/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Infections and infestations EMPYEMA	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Infections and infestations ENCEPHALITIS MENINGOCOCCAL	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Infections and infestations ERYSIPELAS	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Infections and infestations ESCHERICHIA SEPSIS	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Infections and infestations GASTROENTERITIS	0.24% 2/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Infections and infestations HAEMATOMA INFECTION	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Infections and infestations HERPES ZOSTER	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.24% 2/826 • Day 1 up to 12 months
Infections and infestations LOBAR PNEUMONIA	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Infections and infestations LOWER RESPIRATORY TRACT INFECTION	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Infections and infestations ORCHITIS	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Infections and infestations OSTEOMYELITIS	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Infections and infestations PERIRECTAL ABSCESS	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Infections and infestations PNEUMONIA	0.60% 5/840 • Day 1 up to 12 months	0.37% 3/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Infections and infestations PYELONEPHRITIS	0.00% 0/840 • Day 1 up to 12 months	0.25% 2/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Infections and infestations RESPIRATORY TRACT INFECTION	0.00% 0/840 • Day 1 up to 12 months	0.37% 3/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Infections and infestations SALPINGITIS	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Infections and infestations SEPSIS	0.00% 0/840 • Day 1 up to 12 months	0.25% 2/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Infections and infestations SINUSITIS	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Infections and infestations TONSILLITIS	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Infections and infestations URINARY TRACT INFECTION	0.12% 1/840 • Day 1 up to 12 months	0.25% 2/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Infections and infestations VIRAL INFECTION	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Infections and infestations VIRAL SINUSITIS	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications ACCIDENTAL EXPOSURE	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications ANKLE FRACTURE	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications CONCUSSION	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications FEMUR FRACTURE	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications FOREIGN BODY	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications FRACTURED SACRUM	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications HAND FRACTURE	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications HEAT EXHAUSTION	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications HIP FRACTURE	0.24% 2/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications HUMERUS FRACTURE	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications INCISIONAL HERNIA	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications JOINT INJURY	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications LACERATION	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications LIGAMENT RUPTURE	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications LIMB INJURY	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications LOWER LIMB FRACTURE	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications LUMBAR VERTEBRAL FRACTURE	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications MENISCUS LESION	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications OVERDOSE	0.12% 1/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications POST PROCEDURAL HAEMATOMA	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications POST PROCEDURAL HAEMORRHAGE	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications RADIUS FRACTURE	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications SPINAL COMPRESSION FRACTURE	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications SPINAL FRACTURE	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications THERMAL BURN	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications TOXICITY TO VARIOUS AGENTS	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications WOUND HAEMORRHAGE	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Injury, poisoning and procedural complications WRIST FRACTURE	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Investigations BIOPSY BONE	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Investigations COAGULATION TIME PROLONGED	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Investigations PLATELET COUNT DECREASED	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Metabolism and nutrition disorders DEHYDRATION	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Metabolism and nutrition disorders DIABETES MELLITUS	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Metabolism and nutrition disorders ELECTROLYTE IMBALANCE	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Metabolism and nutrition disorders HYPERGLYCAEMIA	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Metabolism and nutrition disorders HYPONATRAEMIA	0.00% 0/840 • Day 1 up to 12 months	0.25% 2/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Musculoskeletal and connective tissue disorders ARTHRALGIA	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Musculoskeletal and connective tissue disorders ARTHRITIS	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Musculoskeletal and connective tissue disorders INTERVERTEBRAL DISC DEGENERATION	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Musculoskeletal and connective tissue disorders INTERVERTEBRAL DISC PROTRUSION	0.12% 1/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Musculoskeletal and connective tissue disorders JOINT ANKYLOSIS	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Musculoskeletal and connective tissue disorders LIGAMENT DISORDER	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Musculoskeletal and connective tissue disorders LUMBAR SPINAL STENOSIS	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL CHEST PAIN	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Musculoskeletal and connective tissue disorders OSTEOARTHRITIS	0.36% 3/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.36% 3/826 • Day 1 up to 12 months
Musculoskeletal and connective tissue disorders PSORIATIC ARTHROPATHY	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Musculoskeletal and connective tissue disorders RHEUMATOID ARTHRITIS	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Musculoskeletal and connective tissue disorders ROTATOR CUFF SYNDROME	0.12% 1/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Musculoskeletal and connective tissue disorders SCOLIOSIS	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Musculoskeletal and connective tissue disorders TENDONITIS	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BASAL CELL CARCINOMA	0.24% 2/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BENIGN PANCREATIC NEOPLASM	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BREAST CANCER	0.12% 1/840 • Day 1 up to 12 months	0.25% 2/811 • Day 1 up to 12 months	0.36% 3/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) CARCINOID TUMOUR	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) CERVIX CARCINOMA	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) COLON ADENOMA	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) COLON CANCER	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) COLON CANCER METASTATIC	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) ENDOMETRIAL CANCER	0.12% 1/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) GASTROINTESTINAL CARCINOMA	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) GASTROINTESTINAL STROMAL TUMOUR	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) LIP AND/OR ORAL CAVITY CANCER	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) LIPOMA	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) LUNG ADENOCARCINOMA	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) LUNG NEOPLASM MALIGNANT	0.24% 2/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) MALIGNANT MELANOMA	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) METASTASES TO BONE	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) METASTATIC BRONCHIAL CARCINOMA	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) METASTATIC NEOPLASM	0.36% 3/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) MULTIPLE MYELOMA	0.12% 1/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) MYELODYSPLASTIC SYNDROME	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) NON-HODGKIN'S LYMPHOMA RECURRENT	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) OVARIAN ADENOMA	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) OVARIAN NEOPLASM	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) PANCREATIC NEOPLASM	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) PROSTATE CANCER	0.24% 2/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) RECTAL CANCER RECURRENT	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) RENAL CANCER	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) SKIN CANCER	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) SQUAMOUS CELL CARCINOMA OF SKIN	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) THYROID CANCER	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) UTERINE LEIOMYOMA	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) VOCAL CORD NEOPLASM	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Nervous system disorders CEREBRAL HAEMORRHAGE	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Nervous system disorders CEREBROVASCULAR ACCIDENT	0.12% 1/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.36% 3/826 • Day 1 up to 12 months
Nervous system disorders CONVULSION	0.12% 1/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Nervous system disorders DEMYELINATING POLYNEUROPATHY	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Nervous system disorders EPILEPSY	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Nervous system disorders EXTRAPYRAMIDAL DISORDER	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Nervous system disorders FEBRILE CONVULSION	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Nervous system disorders HEADACHE	0.00% 0/840 • Day 1 up to 12 months	0.25% 2/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Nervous system disorders HEMIANOPIA HOMONYMOUS	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Nervous system disorders ISCHAEMIC STROKE	0.12% 1/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.24% 2/826 • Day 1 up to 12 months
Nervous system disorders MIGRAINE	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Nervous system disorders MULTIPLE SCLEROSIS	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Nervous system disorders OPTIC NEURITIS	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Nervous system disorders PRESYNCOPE	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Nervous system disorders SCIATICA	0.24% 2/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Nervous system disorders SYNCOPE	0.12% 1/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Nervous system disorders TRANSIENT ISCHAEMIC ATTACK	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.24% 2/826 • Day 1 up to 12 months
Pregnancy, puerperium and perinatal conditions ABORTION SPONTANEOUS	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Pregnancy, puerperium and perinatal conditions PREGNANCY	0.36% 3/840 • Day 1 up to 12 months	0.49% 4/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Psychiatric disorders ALCOHOLISM	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Psychiatric disorders DELIRIUM	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Psychiatric disorders DEPRESSION	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Psychiatric disorders DRUG DEPENDENCE	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Psychiatric disorders PANIC ATTACK	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Psychiatric disorders SUICIDAL IDEATION	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Renal and urinary disorders CALCULUS URINARY	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Renal and urinary disorders HAEMATURIA	0.00% 0/840 • Day 1 up to 12 months	0.25% 2/811 • Day 1 up to 12 months	0.24% 2/826 • Day 1 up to 12 months
Renal and urinary disorders HYDRONEPHROSIS	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Renal and urinary disorders NEPHROLITHIASIS	0.24% 2/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Renal and urinary disorders RENAL COLIC	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.36% 3/826 • Day 1 up to 12 months
Renal and urinary disorders RENAL FAILURE ACUTE	0.24% 2/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.24% 2/826 • Day 1 up to 12 months
Renal and urinary disorders RENAL IMPAIRMENT	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Renal and urinary disorders URETERIC STENOSIS	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.24% 2/826 • Day 1 up to 12 months
Renal and urinary disorders URINARY RETENTION	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Reproductive system and breast disorders METRORRHAGIA	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Reproductive system and breast disorders OVARIAN CYST	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Respiratory, thoracic and mediastinal disorders ACUTE PULMONARY OEDEMA	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Respiratory, thoracic and mediastinal disorders ALLERGIC GRANULOMATOUS ANGIITIS	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Respiratory, thoracic and mediastinal disorders ASTHMA	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Respiratory, thoracic and mediastinal disorders ASTHMATIC CRISIS	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Respiratory, thoracic and mediastinal disorders BRONCHITIS CHRONIC	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Respiratory, thoracic and mediastinal disorders CHRONIC OBSTRUCTIVE PULMONARY DISEASE	0.36% 3/840 • Day 1 up to 12 months	0.37% 3/811 • Day 1 up to 12 months	0.24% 2/826 • Day 1 up to 12 months
Respiratory, thoracic and mediastinal disorders DYSPNOEA EXERTIONAL	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Respiratory, thoracic and mediastinal disorders EPISTAXIS	0.00% 0/840 • Day 1 up to 12 months	0.25% 2/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Respiratory, thoracic and mediastinal disorders HAEMOPTYSIS	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Respiratory, thoracic and mediastinal disorders LARYNGEAL OEDEMA	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.24% 2/826 • Day 1 up to 12 months
Respiratory, thoracic and mediastinal disorders PLEURISY	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Respiratory, thoracic and mediastinal disorders PLEURITIC PAIN	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Respiratory, thoracic and mediastinal disorders PULMONARY EMBOLISM	0.60% 5/840 • Day 1 up to 12 months	0.37% 3/811 • Day 1 up to 12 months	2.4% 20/826 • Day 1 up to 12 months
Respiratory, thoracic and mediastinal disorders RESPIRATORY DISORDER	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Respiratory, thoracic and mediastinal disorders SLEEP APNOEA SYNDROME	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Skin and subcutaneous tissue disorders DECUBITUS ULCER	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Skin and subcutaneous tissue disorders DIABETIC FOOT	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Social circumstances MISCARRIAGE OF PARTNER	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Social circumstances PREGNANCY OF PARTNER	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Surgical and medical procedures ABORTION INDUCED	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Surgical and medical procedures HOSPITALISATION	0.00% 0/840 • Day 1 up to 12 months	0.25% 2/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Vascular disorders ANEURYSM	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Vascular disorders ARTERIAL DISORDER	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Vascular disorders DEEP VEIN THROMBOSIS	0.36% 3/840 • Day 1 up to 12 months	1.1% 9/811 • Day 1 up to 12 months	4.8% 40/826 • Day 1 up to 12 months
Vascular disorders EMBOLISM VENOUS	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Vascular disorders FEMORAL ARTERY EMBOLISM	0.12% 1/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Vascular disorders HAEMATOMA	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Vascular disorders HYPERTENSIVE CRISIS	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Vascular disorders HYPOTENSION	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Vascular disorders MALIGNANT HYPERTENSION	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Vascular disorders ORTHOSTATIC HYPOTENSION	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Vascular disorders PERIPHERAL VASCULAR DISORDER	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Vascular disorders THROMBOPHLEBITIS SUPERFICIAL	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Vascular disorders THROMBOSIS	0.12% 1/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Vascular disorders VARICOPHLEBITIS	0.00% 0/840 • Day 1 up to 12 months	0.12% 1/811 • Day 1 up to 12 months	0.00% 0/826 • Day 1 up to 12 months
Vascular disorders VENOUS INSUFFICIENCY	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months
Vascular disorders VENOUS THROMBOSIS	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.36% 3/826 • Day 1 up to 12 months
Vascular disorders VENOUS THROMBOSIS LIMB	0.00% 0/840 • Day 1 up to 12 months	0.00% 0/811 • Day 1 up to 12 months	0.12% 1/826 • Day 1 up to 12 months

Other adverse events

Measure	Apixaban 2.5mg n=840 participants at risk Participants received 2.5 mg oral tablet apixaban BID	Apixaban 5mg n=811 participants at risk Participants received 5 mg oral tablet apixaban BID	Placebo n=826 participants at risk Participants received oral tablet of placebo BID
Gastrointestinal disorders CONSTIPATION	2.1% 18/840 • Day 1 up to 12 months	1.5% 12/811 • Day 1 up to 12 months	1.7% 14/826 • Day 1 up to 12 months
Gastrointestinal disorders DIARRHOEA	4.4% 37/840 • Day 1 up to 12 months	3.0% 24/811 • Day 1 up to 12 months	2.9% 24/826 • Day 1 up to 12 months
Gastrointestinal disorders NAUSEA	2.4% 20/840 • Day 1 up to 12 months	2.2% 18/811 • Day 1 up to 12 months	2.4% 20/826 • Day 1 up to 12 months
General disorders FATIGUE	2.0% 17/840 • Day 1 up to 12 months	1.7% 14/811 • Day 1 up to 12 months	1.2% 10/826 • Day 1 up to 12 months
General disorders OEDEMA PERIPHERAL	3.3% 28/840 • Day 1 up to 12 months	3.1% 25/811 • Day 1 up to 12 months	4.0% 33/826 • Day 1 up to 12 months
Infections and infestations BRONCHITIS	2.9% 24/840 • Day 1 up to 12 months	3.7% 30/811 • Day 1 up to 12 months	1.6% 13/826 • Day 1 up to 12 months
Infections and infestations INFLUENZA	2.1% 18/840 • Day 1 up to 12 months	2.5% 20/811 • Day 1 up to 12 months	2.4% 20/826 • Day 1 up to 12 months
Infections and infestations NASOPHARYNGITIS	4.9% 41/840 • Day 1 up to 12 months	3.8% 31/811 • Day 1 up to 12 months	4.8% 40/826 • Day 1 up to 12 months
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	2.1% 18/840 • Day 1 up to 12 months	2.2% 18/811 • Day 1 up to 12 months	2.2% 18/826 • Day 1 up to 12 months
Infections and infestations URINARY TRACT INFECTION	3.3% 28/840 • Day 1 up to 12 months	3.7% 30/811 • Day 1 up to 12 months	4.1% 34/826 • Day 1 up to 12 months
Investigations BLOOD CREATINE PHOSPHOKINASE INCREASED	3.1% 26/840 • Day 1 up to 12 months	2.5% 20/811 • Day 1 up to 12 months	2.5% 21/826 • Day 1 up to 12 months
Musculoskeletal and connective tissue disorders ARTHRALGIA	3.8% 32/840 • Day 1 up to 12 months	2.6% 21/811 • Day 1 up to 12 months	2.7% 22/826 • Day 1 up to 12 months
Musculoskeletal and connective tissue disorders BACK PAIN	3.2% 27/840 • Day 1 up to 12 months	5.5% 45/811 • Day 1 up to 12 months	2.9% 24/826 • Day 1 up to 12 months
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	2.5% 21/840 • Day 1 up to 12 months	2.0% 16/811 • Day 1 up to 12 months	1.6% 13/826 • Day 1 up to 12 months
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	5.2% 44/840 • Day 1 up to 12 months	6.4% 52/811 • Day 1 up to 12 months	6.5% 54/826 • Day 1 up to 12 months
Nervous system disorders DIZZINESS	2.4% 20/840 • Day 1 up to 12 months	2.2% 18/811 • Day 1 up to 12 months	1.8% 15/826 • Day 1 up to 12 months
Nervous system disorders HEADACHE	5.2% 44/840 • Day 1 up to 12 months	5.1% 41/811 • Day 1 up to 12 months	5.1% 42/826 • Day 1 up to 12 months
Respiratory, thoracic and mediastinal disorders COUGH	2.5% 21/840 • Day 1 up to 12 months	2.6% 21/811 • Day 1 up to 12 months	2.2% 18/826 • Day 1 up to 12 months
Respiratory, thoracic and mediastinal disorders DYSPNOEA	2.1% 18/840 • Day 1 up to 12 months	1.8% 15/811 • Day 1 up to 12 months	2.3% 19/826 • Day 1 up to 12 months
Respiratory, thoracic and mediastinal disorders EPISTAXIS	1.5% 13/840 • Day 1 up to 12 months	3.3% 27/811 • Day 1 up to 12 months	0.97% 8/826 • Day 1 up to 12 months
Skin and subcutaneous tissue disorders RASH	2.1% 18/840 • Day 1 up to 12 months	0.99% 8/811 • Day 1 up to 12 months	1.5% 12/826 • Day 1 up to 12 months
Vascular disorders DEEP VEIN THROMBOSIS	1.4% 12/840 • Day 1 up to 12 months	0.99% 8/811 • Day 1 up to 12 months	2.8% 23/826 • Day 1 up to 12 months
Vascular disorders HYPERTENSION	4.0% 34/840 • Day 1 up to 12 months	2.3% 19/811 • Day 1 up to 12 months	1.7% 14/826 • Day 1 up to 12 months

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: Clinical.Trials@bms.com

Results disclosure agreements

• Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
• Publication restrictions are in place

Restriction type: OTHER