Trial Outcomes & Findings for Trial to Evaluate Anticoagulation Therapy in Hemodialysis Patients With Atrial Fibrillation (NCT NCT02942407)

NCT ID: NCT02942407

Last Updated: 2020-12-29

Results Overview

Assess the safety of apixaban versus warfarin regarding ISTH major bleeding or clinically relevant non-major bleeding events in patients with NVAF (nonvalvular atrial fibrillation) and ESRD (end-stage renal disease) on hemodialysis. Major bleeding event is defined as:Acute clinically overt bleeding (including access site related bleeding) accompanied by 1 or more of the following: Decrease in Hgb of 2g/dL or more with overt bleeding; Transfusion of 2 or more units of packed RBCs in the setting of an overt bleeding event; Bleeding within a critical site. Hemorrhagic stroke (primary or infarction with hemorrhagic conversion) were classified as major bleeds. Non-major bleeding event is defined as: Acute or sub-acute clinically overt bleeding (including access site related bleeding) that does not meet criteria for major bleeding \& results in Hospital admission for bleeding, physician guided medical or surgical treatment for bleeding, or change in antithrombotic therapy

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 154 participants
• Primary outcome timeframe: Randomization up to Month 15/Final Visit
• Results posted on: 2020-12-29

Participant Flow

Participants who met protocol inclusion criteria were enrolled (randomized 1:1 apixaban and warfarin) at clinical sites across the United States.

Participant milestones

Measure	Apixaban apixaban 5 mg twice daily (apixaban 2.5 mg twice daily for selected patients; \>= 80 years old or dry body weight/hemodialysis target body weight \<= 60 kg) apixaban: oral anticoagulant	Warfarin warfarin as prescribed by participant's provider dose adjusted to target International Normalized Ratio (INR) of 2-3 warfarin: oral anticoagulant
Overall Study STARTED	82	72
Overall Study COMPLETED	56	48
Overall Study NOT COMPLETED	26	24

Reasons for withdrawal

Measure	Apixaban apixaban 5 mg twice daily (apixaban 2.5 mg twice daily for selected patients; \>= 80 years old or dry body weight/hemodialysis target body weight \<= 60 kg) apixaban: oral anticoagulant	Warfarin warfarin as prescribed by participant's provider dose adjusted to target International Normalized Ratio (INR) of 2-3 warfarin: oral anticoagulant
Overall Study Lost to Follow-up	3	2
Overall Study Withdrawal by Subject	7	9
Overall Study Death	16	13

Baseline Characteristics

Trial to Evaluate Anticoagulation Therapy in Hemodialysis Patients With Atrial Fibrillation

Baseline characteristics by cohort

Measure	Apixaban n=82 Participants apixaban 5 mg twice daily (apixaban 2.5 mg twice daily for selected patients) apixaban: oral anticoagulant	Warfarin n=72 Participants warfarin daily dose adjusted to target International Normalized Ratio (INR) of 2-3 warfarin: oral anticoagulant	Total n=154 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	32 Participants n=5 Participants	25 Participants n=7 Participants	57 Participants n=5 Participants
Age, Categorical >=65 years	50 Participants n=5 Participants	47 Participants n=7 Participants	97 Participants n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants	22 Participants n=7 Participants	56 Participants n=5 Participants
Sex: Female, Male Male	48 Participants n=5 Participants	50 Participants n=7 Participants	98 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	77 Participants n=5 Participants	67 Participants n=7 Participants	144 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	35 Participants n=5 Participants	33 Participants n=7 Participants	68 Participants n=5 Participants
Race (NIH/OMB) White	43 Participants n=5 Participants	36 Participants n=7 Participants	79 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	82 Participants n=5 Participants	72 Participants n=7 Participants	154 Participants n=5 Participants
Weight	87.6 kilograms STANDARD_DEVIATION 24.1 • n=5 Participants	93.7 kilograms STANDARD_DEVIATION 24.9 • n=7 Participants	90.5 kilograms STANDARD_DEVIATION 24.6 • n=5 Participants

PRIMARY outcome

Timeframe: Randomization up to Month 15/Final Visit

Population: Intent to Treat Population(ITT): Consists of all unique randomized participants regardless of their compliance with the study protocol. Participants are analyzed in the treatment group to which they were randomized.

Assess the safety of apixaban versus warfarin regarding ISTH major bleeding or clinically relevant non-major bleeding events in patients with NVAF (nonvalvular atrial fibrillation) and ESRD (end-stage renal disease) on hemodialysis.

Major bleeding event is defined as:Acute clinically overt bleeding (including access site related bleeding) accompanied by 1 or more of the following: Decrease in Hgb of 2g/dL or more with overt bleeding; Transfusion of 2 or more units of packed RBCs in the setting of an overt bleeding event; Bleeding within a critical site. Hemorrhagic stroke (primary or infarction with hemorrhagic conversion) were classified as major bleeds.

Non-major bleeding event is defined as: Acute or sub-acute clinically overt bleeding (including access site related bleeding) that does not meet criteria for major bleeding & results in Hospital admission for bleeding, physician guided medical or surgical treatment for bleeding, or change in antithrombotic therapy

Outcome measures

Measure	Apixaban n=82 Participants apixaban 5 mg twice daily (apixaban 2.5 mg twice daily for selected patients; \>= 80 years old or dry body weight/hemodialysis target body weight \<= 60 kg) apixaban: oral anticoagulant	Warfarin n=72 Participants warfarin as prescribed by participant's provider dose adjusted to target International Normalized Ratio (INR) of 2-3 warfarin: oral anticoagulant
Number of Participants Experiencing ISTH (International Society on Thrombosis and Haemostasis) Major or Clinically Relevant Non-major Bleeding	21 Participants	16 Participants

SECONDARY outcome

Timeframe: Randomization up to Month 15/Final Visit

Population: Intent to Treat Population (ITT): Consists of all unique randomized participants regardless of their compliance with the study protocol. Participants are analyzed in the treatment group to which they were randomized.

Number of participants experiencing adjudicated stroke or systemic embolism.

Outcome measures

Measure	Apixaban n=82 Participants apixaban 5 mg twice daily (apixaban 2.5 mg twice daily for selected patients; \>= 80 years old or dry body weight/hemodialysis target body weight \<= 60 kg) apixaban: oral anticoagulant	Warfarin n=72 Participants warfarin as prescribed by participant's provider dose adjusted to target International Normalized Ratio (INR) of 2-3 warfarin: oral anticoagulant
Number of Participants Experiencing Stroke or Systemic Embolism	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Randomization up to Month 15/Final Visit

Population: Intent to Treat Population(ITT): Consists of all unique randomized participants regardless of their compliance with the study protocol. Participants are analyzed in the treatment group to which they were randomized..

Evaluate mortality rates for those participants randomized to warfarin and apixaban in patients with NVAF and ESRD on hemodialysis

Outcome measures

Measure	Apixaban n=82 Participants apixaban 5 mg twice daily (apixaban 2.5 mg twice daily for selected patients; \>= 80 years old or dry body weight/hemodialysis target body weight \<= 60 kg) apixaban: oral anticoagulant	Warfarin n=72 Participants warfarin as prescribed by participant's provider dose adjusted to target International Normalized Ratio (INR) of 2-3 warfarin: oral anticoagulant
Number of Participants Experiencing Mortality	21 Participants	13 Participants

SECONDARY outcome

Timeframe: Randomization up to Month 15/Final Visit

Population: Consists of all unique participants who took at least one dose of the randomized study drug. Participants were analyzed as randomized.

Evaluate days between time from initiation to discontinuation of randomized therapy.

Outcome measures

Measure	Apixaban n=77 Participants apixaban 5 mg twice daily (apixaban 2.5 mg twice daily for selected patients; \>= 80 years old or dry body weight/hemodialysis target body weight \<= 60 kg) apixaban: oral anticoagulant	Warfarin n=68 Participants warfarin as prescribed by participant's provider dose adjusted to target International Normalized Ratio (INR) of 2-3 warfarin: oral anticoagulant
Persistence of Therapy	304.4 Days Standard Deviation 140.0	279.6 Days Standard Deviation 138.2

SECONDARY outcome

Timeframe: 0-12 hours post-dose

Population: Participants in the Apixaban group who had a plasma sample collected. This outcome measure is not relevant to the Warfarin group.

Evaluate the pharmacokinetics of apixaban in ESRD NVAF patients on hemodialysis. The measurement was done from 0-12 hours after the dose was given on Day 1.

Outcome measures

Measure	Apixaban n=20 Participants apixaban 5 mg twice daily (apixaban 2.5 mg twice daily for selected patients; \>= 80 years old or dry body weight/hemodialysis target body weight \<= 60 kg) apixaban: oral anticoagulant	Warfarin n=41 Participants warfarin as prescribed by participant's provider dose adjusted to target International Normalized Ratio (INR) of 2-3 warfarin: oral anticoagulant
Apixaban Plasma Concentration, Cmax	59.7 ng/mL Geometric Coefficient of Variation 34.3	97.9 ng/mL Geometric Coefficient of Variation 37.9

SECONDARY outcome

Timeframe: 0-12 hours post-dose

Population: Participants in the Apixaban group who had a plasma sample collected. This outcome measure is not relevant to the Warfarin group.

Evaluate the pharmacokinetics of apixaban in ESRD NVAF patients on hemodialysis. The measurement was done from 0-12 hours after the dose was given on Day 1.

Outcome measures

Measure	Apixaban n=20 Participants apixaban 5 mg twice daily (apixaban 2.5 mg twice daily for selected patients; \>= 80 years old or dry body weight/hemodialysis target body weight \<= 60 kg) apixaban: oral anticoagulant	Warfarin n=41 Participants warfarin as prescribed by participant's provider dose adjusted to target International Normalized Ratio (INR) of 2-3 warfarin: oral anticoagulant
Apixaban Plasma Concentration, Cmin	28.2 ng/mL Geometric Coefficient of Variation 62.1	49.7 ng/mL Geometric Coefficient of Variation 57.1

SECONDARY outcome

Timeframe: 0-12 hours post-dose

Population: Participants in the Apixaban group who had a plasma sample collected. This outcome measure is not relevant to the Warfarin group.

Evaluate the pharmacokinetics of apixaban in ESRD NVAF patients on hemodialysis. The measurement was done from 0 to 12 hours after dose was given on Day 1.

Outcome measures

Measure	Apixaban n=20 Participants apixaban 5 mg twice daily (apixaban 2.5 mg twice daily for selected patients; \>= 80 years old or dry body weight/hemodialysis target body weight \<= 60 kg) apixaban: oral anticoagulant	Warfarin n=41 Participants warfarin as prescribed by participant's provider dose adjusted to target International Normalized Ratio (INR) of 2-3 warfarin: oral anticoagulant
Area Under the Plasma Apixaban Concentration Curve From 0 to 12 Hours After Dose (AUCO-12)	507 ng*h/mL Geometric Coefficient of Variation 40.4	868 ng*h/mL Geometric Coefficient of Variation 44

SECONDARY outcome

Timeframe: Baseline: Day 3, 4, or 5; Day 28

Population: Data not collected.

Evaluate the pharmacodynamics of apixaban in ESRD NVAF patients on hemodialysis

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 15/Final Visit

Population: Participants who reported medication compliance at month 15.

Measured by self-reported days of medication compliance over the last 30 days.

Outcome measures

Measure	Apixaban n=28 Participants apixaban 5 mg twice daily (apixaban 2.5 mg twice daily for selected patients; \>= 80 years old or dry body weight/hemodialysis target body weight \<= 60 kg) apixaban: oral anticoagulant	Warfarin n=18 Participants warfarin as prescribed by participant's provider dose adjusted to target International Normalized Ratio (INR) of 2-3 warfarin: oral anticoagulant
Adherence to Treatment With Apixaban or With Warfarin 5 days or fewer	1 Participants	1 Participants
Adherence to Treatment With Apixaban or With Warfarin 6 to 23 days	4 Participants	2 Participants
Adherence to Treatment With Apixaban or With Warfarin 24 days or more	23 Participants	15 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Randomization up to Month 15/Final Visit

Adjudicated diagnosis of systemic arterial embolism (Non-pulmonary, non-cranial events) will require a positive clinical history consistent with an acute loss of blood flow to a peripheral artery (or arteries), which is supported by evidence of embolism/thrombosis from surgical specimens, autopsy, angiography, vascular imaging, or other objective testing.

Clinical presentation would include:

1. Abrupt development of pain, absent pulses, pallor, and/or paresis in an extremity (at least an entire digit) without previous severe claudication or findings of severe peripheral vascular disease.

2. Renal embolism will be diagnosed when sudden flank pain or a change in renal laboratory findings occurred.

3. Abdominal vascular/visceral embolism was considered definite if acute abdominal symptoms or referred symptoms developed along with a change in abdominal examination or appropriate laboratory values.

Outcome measures

Measure	Apixaban n=82 Participants apixaban 5 mg twice daily (apixaban 2.5 mg twice daily for selected patients; \>= 80 years old or dry body weight/hemodialysis target body weight \<= 60 kg) apixaban: oral anticoagulant	Warfarin n=72 Participants warfarin as prescribed by participant's provider dose adjusted to target International Normalized Ratio (INR) of 2-3 warfarin: oral anticoagulant
Number of Participants Experiencing Systemic Embolism	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Randomization up to Month 15/Final Visit

Adjudcated stroke defined as a new, non-traumatic episode of focal or global neurological dysfunction of sudden onset caused by central nervous system (CNS) vascular injury as a result of hemorrhage or infarction and not due to a readily identifiable non-vascular cause (i.e. brain tumor). CNS includes brain, spinal cord and retina. The required duration of the deficit is ≥ 24 hours.

• Events with neurologic deficit lasting for < 24 hours and an imaging modality showing evidence of an acute stroke will be counted as stroke as well.
• A retinal ischemic event (embolism, infarction) will be considered a stroke

Outcome measures

Measure	Apixaban n=82 Participants apixaban 5 mg twice daily (apixaban 2.5 mg twice daily for selected patients; \>= 80 years old or dry body weight/hemodialysis target body weight \<= 60 kg) apixaban: oral anticoagulant	Warfarin n=72 Participants warfarin as prescribed by participant's provider dose adjusted to target International Normalized Ratio (INR) of 2-3 warfarin: oral anticoagulant
Number of Participants Experiencing Stroke	2 Participants	2 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Randomization up to Month 15/Final Visit

Population: Intent to Treat Population(ITT): Consists of all unique randomized participants regardless of their compliance with the study protocol. Participants are analyzed in the treatment group to which they were randomized.

Evaluate those experiencing stroke, systemic embolism, ISTH major bleeding, or all-cause mortality for those randomized to warfarin and apixaban in patients with NVAF and ESRD on hemodialysis

Definitions of stroke and systemic embolism are provided under the measurement description of the secondary outcomes for each individual event. Definition of major bleed is provided in outcome measurement description of the primary outcome measure.

Outcome measures

Measure	Apixaban n=82 Participants apixaban 5 mg twice daily (apixaban 2.5 mg twice daily for selected patients; \>= 80 years old or dry body weight/hemodialysis target body weight \<= 60 kg) apixaban: oral anticoagulant	Warfarin n=72 Participants warfarin as prescribed by participant's provider dose adjusted to target International Normalized Ratio (INR) of 2-3 warfarin: oral anticoagulant
Number of Participants Experiencing Stroke, Systemic Embolism, Major Bleeding or All-cause Mortality	27 Participants	29 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Analysis of outcomes and treatment effect according to levels of cardiovascular biomarkers at baseline

Outcome measures

Outcome data not reported

Adverse Events

Apixaban

Serious events: 13 serious events

Other events: 4 other events

Deaths: 21 deaths

Warfarin

Serious events: 8 serious events

Other events: 2 other events

Deaths: 13 deaths

Serious adverse events

Measure	Apixaban n=79 participants at risk apixaban 5 mg twice daily (apixaban 2.5 mg twice daily for selected patients; \>= 80 years old or dry body weight/hemodialysis target body weight \<= 60 kg) apixaban: oral anticoagulant	Warfarin n=68 participants at risk warfarin daily dose adjusted to target International Normalized Ratio (INR) of 2-3 warfarin: oral anticoagulant
Blood and lymphatic system disorders Anaemia	0.00% 0/79 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	2.9% 2/68 • Number of events 2 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Cardiac disorders Angina Pectoris	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Cardiac disorders Atrioventricular dissociation	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Cardiac disorders Bradyarrhythmia	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Cardiac disorders Bradycardia	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Cardiac disorders Cardiac tamponade	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Gastrointestinal disorders Diarrhoea	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Gastrointestinal disorders Gastritis	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
General disorders Asthenia	0.00% 0/79 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	1.5% 1/68 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
General disorders Non-cardiac chest pain	0.00% 0/79 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	1.5% 1/68 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Infections and infestations Cellulitis	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Infections and infestations Gangrene	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Infections and infestations Osteomyelitis	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Injury, poisoning and procedural complications Foot fracture	0.00% 0/79 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	1.5% 1/68 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Injury, poisoning and procedural complications Hip fracture	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/79 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	1.5% 1/68 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Injury, poisoning and procedural complications Vena cava injury	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Metabolism and nutrition disorders Failure to thrive	0.00% 0/79 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	1.5% 1/68 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Metabolism and nutrition disorders Hyperkalaemia	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Metabolism and nutrition disorders Hypoglycaemia	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Metabolism and nutrition disorders Metabolic disorder	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/79 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	1.5% 1/68 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Musculoskeletal and connective tissue disorders Myositis	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.00% 0/79 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	1.5% 1/68 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Nervous system disorders Generalized Anxiety Disorder	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Nervous system disorders Syncope	0.00% 0/79 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	1.5% 1/68 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Renal and urinary disorders Bladder spasm	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/79 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	1.5% 1/68 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/79 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	1.5% 1/68 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/79 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	1.5% 1/68 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Respiratory, thoracic and mediastinal disorders Pulmonary Mass	0.00% 0/79 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	1.5% 1/68 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/79 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	1.5% 1/68 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.00% 0/79 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	1.5% 1/68 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Respiratory, thoracic and mediastinal disorders Tracheal stenosis	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Vascular disorders Hypotension	0.00% 0/79 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	1.5% 1/68 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Vascular disorders Peripheral arterial occlusive disease	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Vascular disorders Peripheral arterly occlusion	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).

Other adverse events

Measure	Apixaban n=79 participants at risk apixaban 5 mg twice daily (apixaban 2.5 mg twice daily for selected patients; \>= 80 years old or dry body weight/hemodialysis target body weight \<= 60 kg) apixaban: oral anticoagulant	Warfarin n=68 participants at risk warfarin daily dose adjusted to target International Normalized Ratio (INR) of 2-3 warfarin: oral anticoagulant
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Blood and lymphatic system disorders Anaemia	0.00% 0/79 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	1.5% 1/68 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Musculoskeletal and connective tissue disorders Myalgia	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
General disorders Catheter site haemorrhage	1.3% 1/79 • Number of events 1 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	0.00% 0/68 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).
Investigations International normalised ratio abnormal	0.00% 0/79 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).	1.5% 1/68 • Number of events 5 • Informed Consent date through 30 days after permanent drug discontinuation. For the apixaban group, 79 of the 82 participants randomized were assessed for adverse events. For the warfarin group, 68 of the 72 participants randomized were assessed for adverse events. The participants that were not assessed for adverse events either died on the same day as randomization (n=1) or withdrew consent for additional follow-up on Day 1 and, therefore, were not assessed for AEs. (n=6).

Additional Information

Christopher Granger, MD

Duke Universitey

Phone: 919-668-8900

Email: christopher.granger@duke.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place