Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial

• Sponsor: Columbia University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00041938
• Collaborator: National Institute of Neurological Disorders and Stroke (NINDS) (NIH)
• Enrollment: 2,305
• Locations: 64
• Arms: 2
• Duration (Months): 141
• Patients Per Site: 36
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to determine which of two treatments, Warfarin or aspirin, is better for preventing death and stroke in patients with poor heart function.

We are now transitioning into the sub-analysis part of the WARCEF patient data.

The study has recently completed data analysis for its Primary Aim. All randomized patients have completed their follow up. All study related procedure as per the protocol has been completed. We are now in the extension phase of the study to obtain more patient data to address further aims of the study. No new procedures are performed and data already in place at the sites will be collected (EKG and echocardiograms).

The aims for this study extension are:

• To assess progression of cardiac dysfunction over time among heart failure patients

• To correlate prognosis with cardiac dysfunction

Condition or Disease	Intervention/Treatment	Phase
Heart Disease; Stroke; Ischemic Heart Disease; Myocardial Infarction	Drug: aspirin; Drug: Warfarin	Phase 3

Detailed Description

Warfarin has proven effective in patients with ischemic heart disease, especially in the reduction of stroke, death and re-infarction following myocardial infarction, and in the reduction of stroke in atrial fibrillation. Warfarin is the most promising unstudied intervention in patients with cardiac failure. This randomized, double-blind, multi-center study will define optimal antithrombotic therapy for patients with cardiac (heart) failure and patients with low ejection fraction (EF). EF is the proportion of left ventricular volume emptied during systole. It reliably measures left ventricular systolic function.

With the rapidly increasing numbers of elderly patients with heart failure, this study has important public health implications. The study will determine which of two commonly used treatments Warfarin, an anticoagulant, or aspirin, a drug which affects platelet function is better for preventing death and stroke in patients with low ejection fraction.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2305 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial
• Study Start Date: Oct 1, 2002
• Actual Primary Completion Date: Aug 1, 2011
• Actual Study Completion Date: Jul 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: aspirin Aspirin: 325 mg per day	Drug: aspirin; 325 mg per day
Active Comparator: warfarin Warfarin: International Normalized Ratio (INR) 2.5-3.0; target INR 2.75	Drug: Warfarin; INR 2.5-3.0; target INR 2.75

Outcome Measures

Primary Outcome Measures

1. Event Rate Per 100 Patient Years for Composite Endpoint of Ischemic Stroke, Intracerebral Hemorrhage, or Death [From date of randomization until the date of the first to occur of ischemic stroke, intracerebral hemorrhage, or death, up to 6 years]

   The time, in years, from randomization to the first to occur of ischemic stroke, intracerebral hemorrhage, or death, up to a maximum of 6 years. Event rate per 100 patient years = 100*(number of subjects with event)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.

Secondary Outcome Measures

1. Event Rate Per 100 Patient-years for Composite Endpoint of Hospitalization for Heart Failure, Myocardial Infarction, Ischemic Stroke, Intracerebral Hemorrhage, or Death. [From randomization to the first to occur of hospitalization for heart failure, myocardial infarction, ischemic stroke, intracerebral hemorrhage, or death, up to a maximum of 6 years.]

   The time, in years, from date of randomization to the date of the first to occur of hospitalization for heart failure, myocardial infarction, ischemic stroke, intracerebral hemorrhage, or death, up to 6 years. Event rate per 100 patient years = 100*(number of subjects with event)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.

Other Outcome Measures

1. Event Rate Per 100 Patient-years for Ischemic Stroke [From date of randomization to date of ischemic stroke component of primary composite outcome, up to 6 years]

   Time, in years, from date of randomization to date of ischemic stroke component of primary composite outcome, up to 6 years. Event rate per 100 patient years = 100*(number of subjects with ischemic stroke)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.

2. Event Rate Per 100 Patient-years for Intracerebral Hemorrhage [From date of randomization to date of intracerebral hemorrhage component of primary composite outcome, up to 6 years]

   Time, in years, from date of randomization to date of intracerebral hemorrhage component of primary composite outcome. Event rate per 100 patient years = 100*(number of subjects with intracerebral hemorrhage)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.

3. Event Rate Per 100 Patient-years for Death [From date of randomization to date of death component of primary composite outcome, up to 6 years]

   Time, in years, from date of randomization to date of death component of primary composite outcome. Event rate per 100 patient years = 100*(number of subjects who died)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.

4. Event Rate Per 100 Patient Years of Myocardial Infarction Component of Secondary Composite Outcome [From date of randomization to date of myocardial infarction component of secondary composite outcome, up to 6 years]

   Time, in years, from date of randomization to date of myocardial infarction, up to 6 years. Includes only myocardial infarctions that occurred during follow-up, before any heart failure hospitalization. Event rate per 100 patient years = 100*(number of subjects with myocardial infarction)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.

5. Event Rate Per 100 Patient Years of Heart Failure Hospitalization Component of Secondary Composite Outcome. [From date of randomization to date of heart failure hospitalization component of secondary composite outcome, up to 6 years]

   Time, in years, from date of randomization to date of heart failure hospitalization, up to 6 years. Includes hospitalizations for heart failure during follow-up that were not preceded by myocardial infarction. Event rate per 100 patient years = 100*(number of subjects with heart failure hospitalization)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.

6. Event Rate Per 100 Patient Years of Ischemic Stroke Component of Secondary Composite Outcome [From date of randomization to date of ischemic stroke component of secondary composite outcome, up to 6 years]

   Ischemic stroke component of secondary composite endpoint. Includes only ischemic strokes that were not preceded by a myocardial infarction or heart failure hospitalization. The number of ischemic strokes that are components of the secondary outcome does not therefore match the number of ischemic strokes that are components of the primary outcome. Event rate per 100 patient years = 100*(number of subjects with ischemic stroke)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1)of all randomized patients / 365.25.

7. Event Rate Per 100 Patient Years of Intracerebral Hemorrhage Component of Secondary Composite Outcome [From date of randomization to date of intracerebral hemorrhage component of secondary composite outcome, up to 6 years]

   Time, in years, from date of randomization to date of intracerebral hemorrhage component of secondary composite outcome. Includes only intracerebral hemorrhages not preceded by myocardial infarction or heart failure hospitalization. Event rate per 100 patient years = 100*(number of subjects with intracerebral hemorrhage)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.

8. Event Rate Per 100 Patient Years of Death Component of Secondary Composite Outcome [From date of randomization to date of death component of secondary composite outcome, up to 6 years]

   Time, in years, from randomization to death component of secondary composite outcome. This measure counts only deaths that were not preceded by heart failure hospitalization, myocardial infarction, ischemic stroke, or intracerebral hemorrhage. Event rate per 100 patient years = 100*(number of subjects who died)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.

9. Rate Per 100 Patient Years of Major Hemorrhage [From date of randomization until end of scheduled follow-up, up to 6 years]

   Rate/100 patient-years of major hemorrhage. Includes all major hemorrhages in any patient. Major hemorrhage was defined as intracerebral, epidural, subdural, subarachnoid, spinal intramedullary, or retinal hemorrhage; any other bleeding causing a decline in the hemoglobin level of more than 2 g per deciliter in 48 hours; or bleeding requiring transfusion of 2 or more units of whole blood, hospitalization, or surgical intervention. Event rate per 100 patient years = 100*(number of major hemorrhage events)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.

10. Rate Per 100 Patient-years of Minor Hemorrhage. [From date of randomization until the end of scheduled follow-up, up to 6 years]

    Rate per 100 patient years of minor hemorrhage. Includes all minor hemorrhages. Minor hemorrhage was defined as any non-major hemorrhage. Event rate per 100 patient years = 100*(number of minor hemorrhage events)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1)of all randomized patients / 365.25.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

• Cardiac EF <=35% by radionuclide ventriculography, left ventriculography or quantitive echocardiographic measurement or an echocardiographic Wall Motion Index of <=1.2, within three months of enrollment. The patient's clinical cardiac state at enrollment should be similar to their state at the time of the qualifying echocardiogram. The qualifying left ventricular function measurement must be obtained at least three months after an MI, coronary bypass grafting, PTCA, and at least one month after pacemaker insertion. Patients scheduled for mitral valve repair should have qualifying echo after surgery.

• Modified Rankin score <=4.

• Patient must be taking ACE inhibitors. If intolerant of ACE inhibitor, patient must be on angiotensin II receptor blockers or hydralazine and nitrates.

• Patient is able to follow an outpatient protocol (requiring monthly blood tests and clinic visits every four months for the duration of the study) and is available by telephone.

• Patient understands the purpose and requirements of the study, can make him/herself understood, and has provided informed consent.

• Patients with recent stroke or TIA within twelve (12) months will be eligible to be included in the recent stroke (RS) subgroup.

• Chronic CHF patients (NYHA I * IV) admitted to the hospital can be randomized prior to discharge if the patient is stable, taking oral medications for 24 hours and ambulatory at the time of discharge. Stable New York Heart Association Class IV patients will be eligible for randomization.

Exclusion Criteria

• The presence of any of the following unequivocal cardiac sources of embolism: chronic or paroxysmal AF, mechanical valve, endocarditis, intracardiac mobile or pedunculated thrombus, and valvular vegetation.

• Cyanotic congenital heart disease, Eisenmenger's syndrome.

• Decompensated heart failure.

• Cardiac surgery, angioplasty, or MI within the past 3 months prior to randomization.

• A contraindication to the use of either warfarin or aspirin, e.g. active peptic ulcer disease, active bleeding diathesis, platelets <100,000*, hematocrit <30, INR >1.3 (if not on warfarin), clotting factor abnormality that increases the risk of bleeding, alcohol or substance abuse, severe gait instability, cerebral hemorrhage, systemic hemorrhage within the past year, severe liver impairment (AST >3x normal*, cirrhosis), any condition requiring regular use of non-steroidal anti-inflammatory agents, allergy to aspirin or warfarin, uncontrolled severe hypertension (systolic pressure >180 mm Hg or diastolic pressure > 110 mm Hg), positive stool guaiac not attributable to hemorrhoids, creatinine >3.0*. *on most recent test done within 30 days prior to randomization

• Patient needs continuing therapy with intravenous heparin or low molecular weight heparin or a specific antiplatelet agent.

• Dementia or psychiatric or physical problem that prevents the patient from following an outpatient program reliably.

• Comorbid conditions that may limit survival to less than five years.

• Pregnancy, or female of childbearing potential who is not sterilized or is not using a medically accepted form of contraception* (see procedure manual). *A pregnancy test is required for all women of childbearing age.

• Enrollment in another study that would conflict with WARCEF.

• Hospitalization for new diagnosis of onset CHF within the past one month or carotid endarterectomy or pacemaker insertion within the past one month prior to randomization .

• Person under 18 years of age.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Southern Arizona Veterans Affairs Medical Center	Tucson	Arizona	United States
2	University of Arizona Health Sciences Center	Tucson	Arizona	United States
3	Santa Clara Medical Center	Santa Clara	California	United States
4	West Los Angeles Veterans Affairs Medical Center	West Los Angeles	California	United States
5	Denver Health Medical Center	Denver	Colorado	United States
6	Denver Veterans Affairs Medical Center	Denver	Colorado	United States
7	George Washington University	Washington	District of Columbia	United States	20037
8	Mayo Clinic Transplant Center	Jacksonville	Florida	United States
9	Melbourne Internal Medicine Associates	Melbourne	Florida	United States
10	Jackson Memorial Hospital/U. of Miami	Miami	Florida	United States
11	Mercy Research Institute	Miami	Florida	United States
12	Cardiovascular Consultants of South Florida	Tamarac	Florida	United States
13	Morehouse School of Medicine	Atlanta	Georgia	United States
14	Northeast Georgia Heart Center	Gainesville	Georgia	United States
15	University of Illinois at Chicago	Chicago	Illinois	United States
16	Methodist Heart, Lung and Vascular Institute	Peoria	Illinois	United States
17	University of Kentucky	Lexington	Kentucky	United States
18	Louisville Veterans Affairs Medical Center	Louisville	Kentucky	United States
19	University of Louisville	Louisville	Kentucky	United States
20	Gulf Regional Research, LLC	Metairie	Louisiana	United States
21	LSU Health Sciences Center	Shreveport	Louisiana	United States
22	Lahey Clinic	Burlington	Massachusetts	United States
23	Veterans Affairs Medical Center	Detroit	Michigan	United States
24	Mercy Health Partners	Muskegon	Michigan	United States
25	Reno Veterans Affairs Medical Center	Reno	Nevada	United States
26	Concord Hospital	Concord	New Hampshire	United States
27	UMDNJ - New Brunswick	New Brunswick	New Jersey	United States
28	University of Medicine and Dentistry of New Jersey	Newark	New Jersey	United States
29	Albany Medical College	Albany	New York	United States
30	Buffalo General Hospital	Buffalo	New York	United States
31	Kaleida Health Millard Fillmore Hospital	Buffalo	New York	United States
32	Five Towns Neuroscience Research	Cedarhurst	New York	United States
33	Long Island Jewish Medical Center	New Hyde Park	New York	United States
34	Columbia University, New York Presbyterian Hospital PH 3-342	New York	New York	United States	10032
35	Columbia University Medical Center	New York	New York	United States
36	Mount Sinai Medical Center	New York	New York	United States
37	Northport Veterans Affairs Medical Center	Northport	New York	United States
38	University of Rochester Medical Center	Rochester	New York	United States
39	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States
40	MetroHealth Medical Center	Cleveland	Ohio	United States
41	Oklahoma City Veterans Affairs Medical Center	Oklahoma City	Oklahoma	United States
42	Lehigh Valley Hospital	Allentown	Pennsylvania	United States
43	Tri-State Medical Group Cardiology	Beaver	Pennsylvania	United States
44	Sewickley Valley Medical Group, Cardiology	Leetsdale	Pennsylvania	United States
45	Albert Einstein Medical Center	Philadelphia	Pennsylvania	United States
46	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States
47	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania	United States
48	Temple University Hospital	Philadelphia	Pennsylvania	United States
49	Black Hills Health Care System	Fort Meade	South Dakota	United States
50	Brooke Army Medical Center MCHE - MDC Cardiology Service	Ft. Sam Houston	Texas	United States
51	Michael E. DeBakey Veterans Affairs Medical Center-MEDVAMC	Houston	Texas	United States
52	Salem VAMC	Salem	Virginia	United States
53	Huntington Veterans Affairs Medical Center	Huntington	West Virginia	United States
54	William S. Middleton Memorial Veterans Hospital	Madison	Wisconsin	United States
55	Center for Neurologic Research	Lethbridge	Alberta	Canada
56	St. Boniface General Hospital	Winnipeg	Manitoba	Canada
57	Saint John Regional Hospital	Saint John	New Brunswick	Canada
58	QE II Health Sciences Centre	Halifax	Nova Scotia	Canada
59	London Health Sciences Centre	London	Ontario	Canada
60	Ottawa Heart Institute	Ottawa	Ontario	Canada
61	Etobicoke Cardiac Research Centre	Rexdale	Ontario	Canada
62	St. Michael's Hospital	Toronto	Ontario	Canada
63	Montreal General Hospital	Montreal	Quebec	Canada
64	Montreal Heart Institute	Montreal	Quebec	Canada

Sponsors and Collaborators

• Columbia University
• National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: Shunichi Homma, M.D., Principal Cardiologist, Associate Chief, Division of Cardiology, and Director, Echocardiography Laboratories Professor of Medicine
• Principal Investigator: Seamus Thompson, PhD, Statistical PI: Clinical Professor of Biostatistics and Neurology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shunichi Homma, Margaret Milliken Hatch Professor of Medicine at the New York-Presbyterian Hospital at the Columbia University Medical Center (In Biomedical Engineering), Columbia University
• ClinicalTrials.gov Identifier: NCT00041938
• Other Study ID Numbers: AAAC1093; U01NS039143-01; R01NS39154; CRC
• First Posted: Jul 22, 2002
• Last Update Posted: Sep 5, 2014
• Last Verified: Aug 1, 2014

• Keywords provided by Shunichi Homma, Margaret Milliken Hatch Professor of Medicine at the New York-Presbyterian Hospital at the Columbia University Medical Center (In Biomedical Engineering), Columbia University: heart disease; stroke; ischemic heart disease; myocardial infarction; atrial fibrillation; low ejection fraction; cardiac failure; aspirin; Warfarin; anticoagulant
• Additional relevant MeSH terms: Myocardial Infarction; Heart Diseases; Myocardial Ischemia; Coronary Artery Disease; Infarction; Aspirin; Warfarin

Study Results

Participant Flow

Recruitment Details	Recruited 2305 patients at 176 sites in 11 countries, between 10/1/2002 and 1/31/2010.
Pre-assignment Detail	Intent-to-treat trial - all randomized patients followed and analyzed.

Arm/Group Title	Aspirin	Warfarin
Arm/Group Description	Aspirin : 325 mg per day	Warfarin : International Normalized Ratio (INR) 2.5-3.0; target INR 2.75
Period Title: Overall Study
STARTED	1163	1142
Completed Follow-up	761	745
Primary Endpoint	320	302
Only Vital Status Known	44	46
Lost to Follow-up	18	17
Withdrew Consent	20	14
COMPLETED	1125	1111
NOT COMPLETED	38	31

Baseline Characteristics

Arm/Group Title	Aspirin	Warfarin	Total
Arm/Group Description	Aspirin : 325 mg per day	Warfarin : INR 2.5-3.0; target INR 2.75	Total of all reporting groups
Overall Participants	1163	1142	2305
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	732 62.9%	706 61.8%	1438 62.4%
>=65 years	431 37.1%	436 38.2%	867 37.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61 (11.1)	61 (11.6)	61 (11.3)
Sex/Gender, Customized (participants) [Number]
Male	936 80.5%	904 79.2%	1840 79.8%
Female	224 19.3%	236 20.7%	460 20%
Unknown	3 0.3%	2 0.2%	5 0.2%
Region of Enrollment (participants) [Number]
North America	546 46.9%	573 50.2%	1119 48.5%
Europe	567 48.8%	527 46.1%	1094 47.5%
Argentina	50 4.3%	42 3.7%	92 4%

Outcome Measures

1. Primary Outcome

Title	Event Rate Per 100 Patient Years for Composite Endpoint of Ischemic Stroke, Intracerebral Hemorrhage, or Death
Description	The time, in years, from randomization to the first to occur of ischemic stroke, intracerebral hemorrhage, or death, up to a maximum of 6 years. Event rate per 100 patient years = 100*(number of subjects with event)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.
Time Frame	From date of randomization until the date of the first to occur of ischemic stroke, intracerebral hemorrhage, or death, up to 6 years

Outcome Measure Data

Analysis Population Description

Intent-to-treat analysis: all enrolled patients were analyzed.

Arm/Group Title	Aspirin	Warfarin
Arm/Group Description	Aspirin : 325 mg per day	Warfarin : INR 2.5-3.0; target INR 2.75
Measure Participants	1163	1142
Number [events per 100 patient-years]	7.93	7.47

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aspirin, Warfarin
	Comments	The primary null hypothesis: time to first event in the composite primary endpoint does not differ significantly between warfarin and aspirin. The original target sample size was 2860, providing 89% power for a log-rank test with two-sided alpha .05, assuming a hazard rate reduction of 17.82% in either group compared with the other, after adjustment for use of beta-blockers and allowance for discontinuation of therapy, dropout, and crossover. The final sample of 2305 patients yielded 69% power.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.40
	Comments	The primary null hypotheses was tested at two-tailed alpha=0.05. A Haybittle-Peto interim monitoring procedure was performed with stopping boundaries for the interim analyses corresponding to a nominal two-tailed P value of 0.001.
	Method	Regression, Cox
	Comments	Cox models stratified by site, New York Heart Association class (I vs. II-IV), and status w/ respect to recent stroke or Transient Ischemic Attack.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.79 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio is for comparison of warfarin vs. aspirin. Warfarin represents the numerator and aspirin represents the denominator of the hazard ratio.

2. Secondary Outcome

Title	Event Rate Per 100 Patient-years for Composite Endpoint of Hospitalization for Heart Failure, Myocardial Infarction, Ischemic Stroke, Intracerebral Hemorrhage, or Death.
Description	The time, in years, from date of randomization to the date of the first to occur of hospitalization for heart failure, myocardial infarction, ischemic stroke, intracerebral hemorrhage, or death, up to 6 years. Event rate per 100 patient years = 100*(number of subjects with event)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.
Time Frame	From randomization to the first to occur of hospitalization for heart failure, myocardial infarction, ischemic stroke, intracerebral hemorrhage, or death, up to a maximum of 6 years.

Outcome Measure Data

Analysis Population Description

Intent-to-treat analysis: all enrolled patients were analyzed.

Arm/Group Title	Aspirin	Warfarin
Arm/Group Description	Aspirin : 325 mg per day	Warfarin : INR 2.5-3.0; target INR 2.75
Measure Participants	1163	1142
Number [events per 100 patient-years]	12.15	12.70

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aspirin, Warfarin
	Comments	Secondary null hypothesis: time to first event in the composite secondary endpoint does not differ significantly between warfarin and aspirin. This was tested at prespecified alpha = 0.05 level, two-tailed.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.33
	Comments	Secondary null hypothesis was tested at two-tailed alpha = 0.05.
	Method	Regression, Cox
	Comments	Cox models stratified by site, New York Heart Association class (I vs. II-IV), and status w/ respect to recent stroke or Transient Ischemic Attack.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.93 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio is for comparison of warfarin vs. aspirin. Warfarin represents the numerator and aspirin represents the denominator of the hazard ratio.

3. Other Pre-specified Outcome

Title	Event Rate Per 100 Patient-years for Ischemic Stroke
Description	Time, in years, from date of randomization to date of ischemic stroke component of primary composite outcome, up to 6 years. Event rate per 100 patient years = 100*(number of subjects with ischemic stroke)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.
Time Frame	From date of randomization to date of ischemic stroke component of primary composite outcome, up to 6 years

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Aspirin	Warfarin
Arm/Group Description	Aspirin : 325 mg per day	Warfarin : INR 2.5-3.0; target INR 2.75
Measure Participants	1163	1142
Number [rate per 100 patient years]	1.36	0.72

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aspirin, Warfarin
	Comments	Null hypothesis: there is no difference between warfarin and aspirin in time to ischemic stroke, adjusting for competing risks of death and intracerebral hemorrhage.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Regression, Cox
	Comments	Cause-specific Cox model, stratified by site, NYHA class (I vs. II, III, or IV), and prior stroke or TIA status.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.52
	Confidence Interval	(2-Sided) 95%; 0.33 to 0.82
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio is for comparison of warfarin vs. aspirin. Warfarin represents the numerator and aspirin represents the denominator of the hazard ratio.

4. Other Pre-specified Outcome

Title	Event Rate Per 100 Patient-years for Intracerebral Hemorrhage
Description	Time, in years, from date of randomization to date of intracerebral hemorrhage component of primary composite outcome. Event rate per 100 patient years = 100*(number of subjects with intracerebral hemorrhage)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.
Time Frame	From date of randomization to date of intracerebral hemorrhage component of primary composite outcome, up to 6 years

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Aspirin	Warfarin
Arm/Group Description	Aspirin : 325 mg per day	Warfarin : INR 2.5-3.0; target INR 2.75
Measure Participants	1163	1142
Number [rate per 100 patient years]	0.05	0.12

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aspirin, Warfarin
	Comments	Null hypothesis: there is no difference between warfarin and aspirin in time to intracerebral hemorrhage, adjusting for competing risks of death and ischemic stroke.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.35
	Comments
	Method	Regression, Cox
	Comments	Cause-specific Cox model, stratified by site, NYHA class (I vs. II, III, or IV), and prior stroke or TIA status.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.22
	Confidence Interval	() 95%; 0.43 to 11.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Other Pre-specified Outcome

Title	Event Rate Per 100 Patient-years for Death
Description	Time, in years, from date of randomization to date of death component of primary composite outcome. Event rate per 100 patient years = 100*(number of subjects who died)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.
Time Frame	From date of randomization to date of death component of primary composite outcome, up to 6 years

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Aspirin	Warfarin
Arm/Group Description	Aspirin : 325 mg per day	Warfarin : INR 2.5-3.0; target INR 2.75
Measure Participants	1163	1142
Number [events per 100 patient-years]	6.52	6.63

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aspirin, Warfarin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.91
	Comments
	Method	Regression, Cox
	Comments	Cause-specific Cox model, stratified by site, NYHA class (I vs. II, III, or IV), and prior stroke or TIA status.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.20
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio is for comparison of warfarin vs. aspirin. Warfarin represents the numerator and aspirin represents the denominator of the hazard ratio.

6. Other Pre-specified Outcome

Title	Event Rate Per 100 Patient Years of Myocardial Infarction Component of Secondary Composite Outcome
Description	Time, in years, from date of randomization to date of myocardial infarction, up to 6 years. Includes only myocardial infarctions that occurred during follow-up, before any heart failure hospitalization. Event rate per 100 patient years = 100*(number of subjects with myocardial infarction)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.
Time Frame	From date of randomization to date of myocardial infarction component of secondary composite outcome, up to 6 years

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Aspirin	Warfarin
Arm/Group Description	Aspirin : 325 mg per day	Warfarin : INR 2.5-3.0; target INR 2.75
Measure Participants	1163	1142
Number [events per 100 patient years]	0.87	0.80

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aspirin, Warfarin
	Comments	Null hypothesis: there is no difference between warfarin and aspirin in time to myocardial infarction, adjusting for competing risks of heart failure hospitalization, ischemic stroke, intracerebral hemorrhage, and death.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.93
	Comments
	Method	Regression, Cox
	Comments	Cause-specific Cox model, stratified by site, NYHA class (I vs. II, III, or IV), and prior stroke or TIA status.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95%; 0.58 to 1.64
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio is for comparison of warfarin vs. aspirin. Warfarin represents the numerator and aspirin represents the denominator of the hazard ratio.

7. Other Pre-specified Outcome

Title	Event Rate Per 100 Patient Years of Heart Failure Hospitalization Component of Secondary Composite Outcome.
Description	Time, in years, from date of randomization to date of heart failure hospitalization, up to 6 years. Includes hospitalizations for heart failure during follow-up that were not preceded by myocardial infarction. Event rate per 100 patient years = 100*(number of subjects with heart failure hospitalization)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.
Time Frame	From date of randomization to date of heart failure hospitalization component of secondary composite outcome, up to 6 years

Outcome Measure Data

Analysis Population Description

Intent-to-treat.

Arm/Group Title	Aspirin	Warfarin
Arm/Group Description	Aspirin : 325 mg per day	Warfarin : INR 2.5-3.0; target INR 2.75
Measure Participants	1163	1142
Number [events per 100 patient years]	5.67	6.79

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aspirin, Warfarin
	Comments	Null hypothesis: there is no difference between warfarin and aspirin in time to heart failure hospitalization, adjusting for competing risks of myocardial infarction, ischemic stroke, intracerebral hemorrhage, and death.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.053
	Comments
	Method	Regression, Cox
	Comments	Cause-specific Cox model, stratified by site, NYHA class (I vs. II, III, or IV), and prior stroke or TIA status.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 95%; 0.998 to 1.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Other Pre-specified Outcome

Title	Event Rate Per 100 Patient Years of Ischemic Stroke Component of Secondary Composite Outcome
Description	Ischemic stroke component of secondary composite endpoint. Includes only ischemic strokes that were not preceded by a myocardial infarction or heart failure hospitalization. The number of ischemic strokes that are components of the secondary outcome does not therefore match the number of ischemic strokes that are components of the primary outcome. Event rate per 100 patient years = 100*(number of subjects with ischemic stroke)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1)of all randomized patients / 365.25.
Time Frame	From date of randomization to date of ischemic stroke component of secondary composite outcome, up to 6 years

Outcome Measure Data

Analysis Population Description

Intent-to-treat.

Arm/Group Title	Aspirin	Warfarin
Arm/Group Description	Aspirin : 325 mg per day	Warfarin : INR 2.5-3.0; target INR 2.75
Measure Participants	1163	1142
Number [events per 100 patient years]	1.14	0.57

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aspirin, Warfarin
	Comments	Null hypothesis: there is no difference between warfarin and aspirin in time to ischemic stroke, adjusting for competing risks of myocardial infarction, heart failure hospitalization, death and intracerebral hemorrhage.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	Regression, Cox
	Comments	Cause-specific Cox model, stratified by site, NYHA class (I vs. II, III, or IV), and prior stroke or TIA status.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 95%; 0.32 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Other Pre-specified Outcome

Title	Event Rate Per 100 Patient Years of Intracerebral Hemorrhage Component of Secondary Composite Outcome
Description	Time, in years, from date of randomization to date of intracerebral hemorrhage component of secondary composite outcome. Includes only intracerebral hemorrhages not preceded by myocardial infarction or heart failure hospitalization. Event rate per 100 patient years = 100*(number of subjects with intracerebral hemorrhage)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.
Time Frame	From date of randomization to date of intracerebral hemorrhage component of secondary composite outcome, up to 6 years

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Aspirin	Warfarin
Arm/Group Description	Aspirin : 325 mg per day	Warfarin : INR 2.5-3.0; target INR 2.75
Measure Participants	1163	1142
Number [events per 100 patient years]	0.06	0.11

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aspirin, Warfarin
	Comments	Null hypothesis: there is no difference between warfarin and aspirin in time to intracerebral hemorrhage, adjusting for competing risks of myocardial infarction, heart failure hospitalization, ischemic stroke, and death.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.51
	Comments
	Method	Regression, Cox
	Comments	Cause-specific Cox model, stratified by site, NYHA class (I vs. II, III, or IV), and prior stroke or TIA status.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.77
	Confidence Interval	(2-Sided) 95%; 0.32 to 9.88
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio is for comparison of warfarin vs. aspirin. Warfarin represents the numerator and aspirin represents the denominator of the hazard ratio.

10. Other Pre-specified Outcome

Title	Event Rate Per 100 Patient Years of Death Component of Secondary Composite Outcome
Description	Time, in years, from randomization to death component of secondary composite outcome. This measure counts only deaths that were not preceded by heart failure hospitalization, myocardial infarction, ischemic stroke, or intracerebral hemorrhage. Event rate per 100 patient years = 100*(number of subjects who died)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.
Time Frame	From date of randomization to date of death component of secondary composite outcome, up to 6 years

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Aspirin	Warfarin
Arm/Group Description	Aspirin : 325 mg per day	Warfarin : INR 2.5-3.0; target INR 2.75
Measure Participants	1163	1142
Number [events per 100 patient years]	4.41	4.43

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aspirin, Warfarin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments
	Method	Regression, Cox
	Comments	Cause-specific Cox model, stratified by site, NYHA class (I vs. II, III, or IV), and prior stroke or TIA status.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.03
	Confidence Interval	() 95%; 0.81 to 1.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Other Pre-specified Outcome

Title	Rate Per 100 Patient Years of Major Hemorrhage
Description	Rate/100 patient-years of major hemorrhage. Includes all major hemorrhages in any patient. Major hemorrhage was defined as intracerebral, epidural, subdural, subarachnoid, spinal intramedullary, or retinal hemorrhage; any other bleeding causing a decline in the hemoglobin level of more than 2 g per deciliter in 48 hours; or bleeding requiring transfusion of 2 or more units of whole blood, hospitalization, or surgical intervention. Event rate per 100 patient years = 100*(number of major hemorrhage events)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.
Time Frame	From date of randomization until end of scheduled follow-up, up to 6 years

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Aspirin	Warfarin
Arm/Group Description	Aspirin : 325 mg per day	Warfarin : INR 2.5-3.0; target INR 2.75
Measure Participants	1163	1142
Number [events per 100 patient years]	0.87	1.78

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aspirin, Warfarin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Poisson
	Comments
Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	2.05
	Confidence Interval	(2-Sided) 95%; 1.36 to 3.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	The warfarin arm represents the numerator and the aspirin arm represents the denominator of the rate ratio.

12. Other Pre-specified Outcome

Title	Rate Per 100 Patient-years of Minor Hemorrhage.
Description	Rate per 100 patient years of minor hemorrhage. Includes all minor hemorrhages. Minor hemorrhage was defined as any non-major hemorrhage. Event rate per 100 patient years = 100*(number of minor hemorrhage events)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1)of all randomized patients / 365.25.
Time Frame	From date of randomization until the end of scheduled follow-up, up to 6 years

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Aspirin	Warfarin
Arm/Group Description	Aspirin : 325 mg per day	Warfarin : INR 2.5-3.0; target INR 2.75
Measure Participants	1163	1142
Number [events per 100 patient-years]	7.34	11.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aspirin, Warfarin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Poisson
	Comments
Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	1.56
	Confidence Interval	() 95%; 1.34 to 1.81
	Parameter Dispersion	Type: Value:
	Estimation Comments	Warfarin group represents the numerator and aspirin group represents denominator of rate ratio.

Adverse Events

Arm/Group Title	Aspirin		Warfarin
Arm/Group Description	Aspirin : 325 mg per day		Warfarin : INR 2.5-3.0; target INR 2.75
All Cause Mortality
	Aspirin		Warfarin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Aspirin		Warfarin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	617/1163 (53.1%)		632/1142 (55.3%)
Blood and lymphatic system disorders
Blood dyscrasia	3/1163 (0.3%)	3	4/1142 (0.4%)	4
BLOOD/BONE MARROW: Other	1/1163 (0.1%)	1	3/1142 (0.3%)	4
Thrombocytopenia/Anemia/Leukopenia	1/1163 (0.1%)	1	12/1142 (1.1%)	12
Hemorrhage/Bleeding	0/1163 (0%)	0	1/1142 (0.1%)	1
LYMPHATICS: Other	1/1163 (0.1%)	1	0/1142 (0%)	0
Peripheral edema	4/1163 (0.3%)	4	4/1142 (0.4%)	4
Cardiac disorders
Atrial fibrillation/Atrial flutter/Supraventricular tachycardia	56/1163 (4.8%)	67	35/1142 (3.1%)	45
Bradycardia	6/1163 (0.5%)	6	6/1142 (0.5%)	6
CARDIAC ARRHYTHMIA: Other	7/1163 (0.6%)	7	3/1142 (0.3%)	3
Ventricular fibrillation	7/1163 (0.6%)	8	15/1142 (1.3%)	17
Ventricular tachycardia	24/1163 (2.1%)	33	39/1142 (3.4%)	46
Acute cardiac failure/CHF/Pulmonary edema	209/1163 (18%)	432	243/1142 (21.3%)	506
AICD firing/discharge	16/1163 (1.4%)	21	20/1142 (1.8%)	21
Angina/Chest pain	70/1163 (6%)	105	88/1142 (7.7%)	148
CARDIAC GENERAL: Other	16/1163 (1.4%)	18	16/1142 (1.4%)	19
Malignant hypertension	3/1163 (0.3%)	3	7/1142 (0.6%)	7
Myocardial infarction/Acute Coronary Syndrome	48/1163 (4.1%)	60	50/1142 (4.4%)	59
Pulmonary embolism	6/1163 (0.5%)	6	5/1142 (0.4%)	5
Endocrine disorders
Diabetes mellitus and its complications	26/1163 (2.2%)	35	22/1142 (1.9%)	35
ENDOCRINE: Other	2/1163 (0.2%)	2	1/1142 (0.1%)	1
Eye disorders
OCULAR/VISUAL: Other	5/1163 (0.4%)	7	3/1142 (0.3%)	5
Gastrointestinal disorders
Gastrointestinal disturbance/Diarrhea/Jaundice/Nausea/Stomach pain/Etc.	54/1163 (4.6%)	70	66/1142 (5.8%)	82
GASTROINTESTINAL: Other	25/1163 (2.1%)	31	17/1142 (1.5%)	18
General disorders
ALLERGY/IMMUNOLOGY: Other	1/1163 (0.1%)	1	1/1142 (0.1%)	1
Laryngeal edema/Allergic reaction/Anaphylaxis/Angioedema/Rash	4/1163 (0.3%)	4	2/1142 (0.2%)	2
CONSTITUTIONAL SYMPTOMS: Other	7/1163 (0.6%)	7	1/1142 (0.1%)	1
Drug abuse	3/1163 (0.3%)	3	1/1142 (0.1%)	1
OTHER: Other	19/1163 (1.6%)	23	32/1142 (2.8%)	33
Pregnancy	0/1163 (0%)	0	1/1142 (0.1%)	1
Suicide attempt/Psychiatric disorder	16/1163 (1.4%)	16	10/1142 (0.9%)	10
PAIN: Other	14/1163 (1.2%)	15	13/1142 (1.1%)	20
Hepatobiliary disorders
Acute hepatic failure	3/1163 (0.3%)	3	3/1142 (0.3%)	3
HEPATOBILIARY/PANCREAS: Other	3/1163 (0.3%)	3	5/1142 (0.4%)	7
Infections and infestations
Infection/Sepsis/Fever	66/1163 (5.7%)	79	79/1142 (6.9%)	97
Metabolism and nutrition disorders
Metabolic disturbance/Gout	14/1163 (1.2%)	15	16/1142 (1.4%)	17
METABOLIC/LABORATORY: Other	12/1163 (1%)	14	10/1142 (0.9%)	11
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL/SOFT TISSUE: Other	39/1163 (3.4%)	43	29/1142 (2.5%)	32
Visceral necrosis	0/1163 (0%)	0	4/1142 (0.4%)	4
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANCY: Other	22/1163 (1.9%)	24	20/1142 (1.8%)	24
Nervous system disorders
Convulsions/Seizures	6/1163 (0.5%)	6	5/1142 (0.4%)	10
NEUROLOGY: Other	8/1163 (0.7%)	8	7/1142 (0.6%)	7
Stroke or TIA	13/1163 (1.1%)	16	15/1142 (1.3%)	16
Syncope/Pre-syncope	41/1163 (3.5%)	48	68/1142 (6%)	83
Renal and urinary disorders
Acute renal failure/Proteinuria	28/1163 (2.4%)	32	33/1142 (2.9%)	36
RENAL/GENITOURINARY: Other	7/1163 (0.6%)	7	7/1142 (0.6%)	7
Reproductive system and breast disorders
SEXUAL/REPRODUCTIVE FUNCTION: Other	2/1163 (0.2%)	2	6/1142 (0.5%)	6
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	7/1163 (0.6%)	8	9/1142 (0.8%)	9
Pulmonary disease/Pneumonia/Bronchitis/Asthma/Breathing difficulties	87/1163 (7.5%)	133	79/1142 (6.9%)	100
PULMONARY/UPPER RESPIRATORY: Other	7/1163 (0.6%)	7	3/1142 (0.3%)	3
Skin and subcutaneous tissue disorders
DERMATOLOGY/SKIN: Other	1/1163 (0.1%)	1	0/1142 (0%)	0
Grade 4 dermatologic manifestations	1/1163 (0.1%)	2	1/1142 (0.1%)	1
Surgical and medical procedures
"Cardiac device implantation (pacemaker, defibrillator, etc.)"	123/1163 (10.6%)	133	109/1142 (9.5%)	118
"Cardiac procedure (stent, catheterization, EP study, ablation, etc.)"	62/1163 (5.3%)	76	66/1142 (5.8%)	82
Cardiac surgery	28/1163 (2.4%)	28	23/1142 (2%)	25
Non-cardiac surgery/Diagnostic surgery	75/1163 (6.4%)	102	57/1142 (5%)	67
SURGERY/INTRA-OPERATIVE INJURY: Other	4/1163 (0.3%)	4	8/1142 (0.7%)	8
Vascular disorders
Systemic embolism	3/1163 (0.3%)	3	5/1142 (0.4%)	5
VASCULAR: Other	16/1163 (1.4%)	17	13/1142 (1.1%)	13
Other (Not Including Serious) Adverse Events
	Aspirin		Warfarin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	749/1163 (64.4%)		799/1142 (70%)
General disorders
All non-serious adverse events	749/1163 (64.4%)	4483	799/1142 (70%)	4895

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.