Trial Outcomes & Findings for Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial (NCT NCT00041938)

NCT ID: NCT00041938

Last Updated: 2014-09-05

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2305 participants

Primary outcome timeframe

From date of randomization until the date of the first to occur of ischemic stroke, intracerebral hemorrhage, or death, up to 6 years

Results posted on

2014-09-05

Participant Flow

Recruited 2305 patients at 176 sites in 11 countries, between 10/1/2002 and 1/31/2010.

Intent-to-treat trial - all randomized patients followed and analyzed.

Participant milestones

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

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Aspirin
n=1163 Participants
Aspirin : 325 mg per day
Warfarin
n=1142 Participants
Warfarin : INR 2.5-3.0; target INR 2.75
Total
n=2305 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
732 Participants
n=5 Participants
706 Participants
n=7 Participants
1438 Participants
n=5 Participants
Age, Categorical
>=65 years
431 Participants
n=5 Participants
436 Participants
n=7 Participants
867 Participants
n=5 Participants
Age, Continuous
61 years
STANDARD_DEVIATION 11.1 • n=5 Participants
61 years
STANDARD_DEVIATION 11.6 • n=7 Participants
61 years
STANDARD_DEVIATION 11.3 • n=5 Participants
Sex/Gender, Customized
Male
936 participants
n=5 Participants
904 participants
n=7 Participants
1840 participants
n=5 Participants
Sex/Gender, Customized
Female
224 participants
n=5 Participants
236 participants
n=7 Participants
460 participants
n=5 Participants
Sex/Gender, Customized
Unknown
3 participants
n=5 Participants
2 participants
n=7 Participants
5 participants
n=5 Participants
Region of Enrollment
North America
546 participants
n=5 Participants
573 participants
n=7 Participants
1119 participants
n=5 Participants
Region of Enrollment
Europe
567 participants
n=5 Participants
527 participants
n=7 Participants
1094 participants
n=5 Participants
Region of Enrollment
Argentina
50 participants
n=5 Participants
42 participants
n=7 Participants
92 participants
n=5 Participants

PRIMARY outcome

Timeframe: From date of randomization until the date of the first to occur of ischemic stroke, intracerebral hemorrhage, or death, up to 6 years

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

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.

Outcome measures

Outcome measures
Measure
Aspirin
n=1163 Participants
Aspirin : 325 mg per day
Warfarin
n=1142 Participants
Warfarin : INR 2.5-3.0; target INR 2.75
Event Rate Per 100 Patient Years for Composite Endpoint of Ischemic Stroke, Intracerebral Hemorrhage, or Death
7.93 events per 100 patient-years
7.47 events per 100 patient-years

SECONDARY outcome

Timeframe: 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.

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

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.

Outcome measures

Outcome measures
Measure
Aspirin
n=1163 Participants
Aspirin : 325 mg per day
Warfarin
n=1142 Participants
Warfarin : INR 2.5-3.0; target INR 2.75
Event Rate Per 100 Patient-years for Composite Endpoint of Hospitalization for Heart Failure, Myocardial Infarction, Ischemic Stroke, Intracerebral Hemorrhage, or Death.
12.15 events per 100 patient-years
12.70 events per 100 patient-years

OTHER_PRE_SPECIFIED outcome

Timeframe: From date of randomization to date of ischemic stroke component of primary composite outcome, up to 6 years

Population: Intent-to-treat

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.

Outcome measures

Outcome measures
Measure
Aspirin
n=1163 Participants
Aspirin : 325 mg per day
Warfarin
n=1142 Participants
Warfarin : INR 2.5-3.0; target INR 2.75
Event Rate Per 100 Patient-years for Ischemic Stroke
1.36 rate per 100 patient years
0.72 rate per 100 patient years

OTHER_PRE_SPECIFIED outcome

Timeframe: From date of randomization to date of intracerebral hemorrhage component of primary composite outcome, up to 6 years

Population: Intent-to-treat

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.

Outcome measures

Outcome measures
Measure
Aspirin
n=1163 Participants
Aspirin : 325 mg per day
Warfarin
n=1142 Participants
Warfarin : INR 2.5-3.0; target INR 2.75
Event Rate Per 100 Patient-years for Intracerebral Hemorrhage
0.05 rate per 100 patient years
0.12 rate per 100 patient years

OTHER_PRE_SPECIFIED outcome

Timeframe: From date of randomization to date of death component of primary composite outcome, up to 6 years

Population: Intent-to-treat

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.

Outcome measures

Outcome measures
Measure
Aspirin
n=1163 Participants
Aspirin : 325 mg per day
Warfarin
n=1142 Participants
Warfarin : INR 2.5-3.0; target INR 2.75
Event Rate Per 100 Patient-years for Death
6.52 events per 100 patient-years
6.63 events per 100 patient-years

OTHER_PRE_SPECIFIED outcome

Timeframe: From date of randomization to date of myocardial infarction component of secondary composite outcome, up to 6 years

Population: Intent-to-treat

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.

Outcome measures

Outcome measures
Measure
Aspirin
n=1163 Participants
Aspirin : 325 mg per day
Warfarin
n=1142 Participants
Warfarin : INR 2.5-3.0; target INR 2.75
Event Rate Per 100 Patient Years of Myocardial Infarction Component of Secondary Composite Outcome
0.87 events per 100 patient years
0.80 events per 100 patient years

OTHER_PRE_SPECIFIED outcome

Timeframe: From date of randomization to date of heart failure hospitalization component of secondary composite outcome, up to 6 years

Population: Intent-to-treat.

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.

Outcome measures

Outcome measures
Measure
Aspirin
n=1163 Participants
Aspirin : 325 mg per day
Warfarin
n=1142 Participants
Warfarin : INR 2.5-3.0; target INR 2.75
Event Rate Per 100 Patient Years of Heart Failure Hospitalization Component of Secondary Composite Outcome.
5.67 events per 100 patient years
6.79 events per 100 patient years

OTHER_PRE_SPECIFIED outcome

Timeframe: From date of randomization to date of ischemic stroke component of secondary composite outcome, up to 6 years

Population: Intent-to-treat.

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.

Outcome measures

Outcome measures
Measure
Aspirin
n=1163 Participants
Aspirin : 325 mg per day
Warfarin
n=1142 Participants
Warfarin : INR 2.5-3.0; target INR 2.75
Event Rate Per 100 Patient Years of Ischemic Stroke Component of Secondary Composite Outcome
1.14 events per 100 patient years
0.57 events per 100 patient years

OTHER_PRE_SPECIFIED outcome

Timeframe: From date of randomization to date of intracerebral hemorrhage component of secondary composite outcome, up to 6 years

Population: Intent-to-treat

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.

Outcome measures

Outcome measures
Measure
Aspirin
n=1163 Participants
Aspirin : 325 mg per day
Warfarin
n=1142 Participants
Warfarin : INR 2.5-3.0; target INR 2.75
Event Rate Per 100 Patient Years of Intracerebral Hemorrhage Component of Secondary Composite Outcome
0.06 events per 100 patient years
0.11 events per 100 patient years

OTHER_PRE_SPECIFIED outcome

Timeframe: From date of randomization to date of death component of secondary composite outcome, up to 6 years

Population: Intent-to-treat

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.

Outcome measures

Outcome measures
Measure
Aspirin
n=1163 Participants
Aspirin : 325 mg per day
Warfarin
n=1142 Participants
Warfarin : INR 2.5-3.0; target INR 2.75
Event Rate Per 100 Patient Years of Death Component of Secondary Composite Outcome
4.41 events per 100 patient years
4.43 events per 100 patient years

OTHER_PRE_SPECIFIED outcome

Timeframe: From date of randomization until end of scheduled follow-up, up to 6 years

Population: Intent-to-treat

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.

Outcome measures

Outcome measures
Measure
Aspirin
n=1163 Participants
Aspirin : 325 mg per day
Warfarin
n=1142 Participants
Warfarin : INR 2.5-3.0; target INR 2.75
Rate Per 100 Patient Years of Major Hemorrhage
0.87 events per 100 patient years
1.78 events per 100 patient years

OTHER_PRE_SPECIFIED outcome

Timeframe: From date of randomization until the end of scheduled follow-up, up to 6 years

Population: Intent-to-treat

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.

Outcome measures

Outcome measures
Measure
Aspirin
n=1163 Participants
Aspirin : 325 mg per day
Warfarin
n=1142 Participants
Warfarin : INR 2.5-3.0; target INR 2.75
Rate Per 100 Patient-years of Minor Hemorrhage.
7.34 events per 100 patient-years
11.6 events per 100 patient-years

Adverse Events

Aspirin

Serious events: 617 serious events
Other events: 749 other events
Deaths: 0 deaths

Warfarin

Serious events: 632 serious events
Other events: 799 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Aspirin
n=1163 participants at risk
Aspirin : 325 mg per day
Warfarin
n=1142 participants at risk
Warfarin : INR 2.5-3.0; target INR 2.75
General disorders
ALLERGY/IMMUNOLOGY: Other
0.09%
1/1163 • Number of events 1
0.09%
1/1142 • Number of events 1
General disorders
Laryngeal edema/Allergic reaction/Anaphylaxis/Angioedema/Rash
0.34%
4/1163 • Number of events 4
0.18%
2/1142 • Number of events 2
Blood and lymphatic system disorders
Blood dyscrasia
0.26%
3/1163 • Number of events 3
0.35%
4/1142 • Number of events 4
Blood and lymphatic system disorders
BLOOD/BONE MARROW: Other
0.09%
1/1163 • Number of events 1
0.26%
3/1142 • Number of events 4
Blood and lymphatic system disorders
Thrombocytopenia/Anemia/Leukopenia
0.09%
1/1163 • Number of events 1
1.1%
12/1142 • Number of events 12
Cardiac disorders
Atrial fibrillation/Atrial flutter/Supraventricular tachycardia
4.8%
56/1163 • Number of events 67
3.1%
35/1142 • Number of events 45
Cardiac disorders
Bradycardia
0.52%
6/1163 • Number of events 6
0.53%
6/1142 • Number of events 6
Cardiac disorders
CARDIAC ARRHYTHMIA: Other
0.60%
7/1163 • Number of events 7
0.26%
3/1142 • Number of events 3
Cardiac disorders
Ventricular fibrillation
0.60%
7/1163 • Number of events 8
1.3%
15/1142 • Number of events 17
Cardiac disorders
Ventricular tachycardia
2.1%
24/1163 • Number of events 33
3.4%
39/1142 • Number of events 46
Cardiac disorders
Acute cardiac failure/CHF/Pulmonary edema
18.0%
209/1163 • Number of events 432
21.3%
243/1142 • Number of events 506
Cardiac disorders
AICD firing/discharge
1.4%
16/1163 • Number of events 21
1.8%
20/1142 • Number of events 21
Cardiac disorders
Angina/Chest pain
6.0%
70/1163 • Number of events 105
7.7%
88/1142 • Number of events 148
Cardiac disorders
CARDIAC GENERAL: Other
1.4%
16/1163 • Number of events 18
1.4%
16/1142 • Number of events 19
Cardiac disorders
Malignant hypertension
0.26%
3/1163 • Number of events 3
0.61%
7/1142 • Number of events 7
Cardiac disorders
Myocardial infarction/Acute Coronary Syndrome
4.1%
48/1163 • Number of events 60
4.4%
50/1142 • Number of events 59
Cardiac disorders
Pulmonary embolism
0.52%
6/1163 • Number of events 6
0.44%
5/1142 • Number of events 5
General disorders
CONSTITUTIONAL SYMPTOMS: Other
0.60%
7/1163 • Number of events 7
0.09%
1/1142 • Number of events 1
Skin and subcutaneous tissue disorders
DERMATOLOGY/SKIN: Other
0.09%
1/1163 • Number of events 1
0.00%
0/1142
Skin and subcutaneous tissue disorders
Grade 4 dermatologic manifestations
0.09%
1/1163 • Number of events 2
0.09%
1/1142 • Number of events 1
Endocrine disorders
Diabetes mellitus and its complications
2.2%
26/1163 • Number of events 35
1.9%
22/1142 • Number of events 35
Endocrine disorders
ENDOCRINE: Other
0.17%
2/1163 • Number of events 2
0.09%
1/1142 • Number of events 1
Gastrointestinal disorders
Gastrointestinal disturbance/Diarrhea/Jaundice/Nausea/Stomach pain/Etc.
4.6%
54/1163 • Number of events 70
5.8%
66/1142 • Number of events 82
Gastrointestinal disorders
GASTROINTESTINAL: Other
2.1%
25/1163 • Number of events 31
1.5%
17/1142 • Number of events 18
Blood and lymphatic system disorders
Hemorrhage/Bleeding
0.00%
0/1163
0.09%
1/1142 • Number of events 1
Hepatobiliary disorders
Acute hepatic failure
0.26%
3/1163 • Number of events 3
0.26%
3/1142 • Number of events 3
Hepatobiliary disorders
HEPATOBILIARY/PANCREAS: Other
0.26%
3/1163 • Number of events 3
0.44%
5/1142 • Number of events 7
Infections and infestations
Infection/Sepsis/Fever
5.7%
66/1163 • Number of events 79
6.9%
79/1142 • Number of events 97
Blood and lymphatic system disorders
LYMPHATICS: Other
0.09%
1/1163 • Number of events 1
0.00%
0/1142
Blood and lymphatic system disorders
Peripheral edema
0.34%
4/1163 • Number of events 4
0.35%
4/1142 • Number of events 4
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANCY: Other
1.9%
22/1163 • Number of events 24
1.8%
20/1142 • Number of events 24
Metabolism and nutrition disorders
Metabolic disturbance/Gout
1.2%
14/1163 • Number of events 15
1.4%
16/1142 • Number of events 17
Metabolism and nutrition disorders
METABOLIC/LABORATORY: Other
1.0%
12/1163 • Number of events 14
0.88%
10/1142 • Number of events 11
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL/SOFT TISSUE: Other
3.4%
39/1163 • Number of events 43
2.5%
29/1142 • Number of events 32
Musculoskeletal and connective tissue disorders
Visceral necrosis
0.00%
0/1163
0.35%
4/1142 • Number of events 4
Nervous system disorders
Convulsions/Seizures
0.52%
6/1163 • Number of events 6
0.44%
5/1142 • Number of events 10
Nervous system disorders
NEUROLOGY: Other
0.69%
8/1163 • Number of events 8
0.61%
7/1142 • Number of events 7
Nervous system disorders
Stroke or TIA
1.1%
13/1163 • Number of events 16
1.3%
15/1142 • Number of events 16
Nervous system disorders
Syncope/Pre-syncope
3.5%
41/1163 • Number of events 48
6.0%
68/1142 • Number of events 83
Eye disorders
OCULAR/VISUAL: Other
0.43%
5/1163 • Number of events 7
0.26%
3/1142 • Number of events 5
General disorders
Drug abuse
0.26%
3/1163 • Number of events 3
0.09%
1/1142 • Number of events 1
General disorders
OTHER: Other
1.6%
19/1163 • Number of events 23
2.8%
32/1142 • Number of events 33
General disorders
Pregnancy
0.00%
0/1163
0.09%
1/1142 • Number of events 1
General disorders
Suicide attempt/Psychiatric disorder
1.4%
16/1163 • Number of events 16
0.88%
10/1142 • Number of events 10
General disorders
PAIN: Other
1.2%
14/1163 • Number of events 15
1.1%
13/1142 • Number of events 20
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
0.60%
7/1163 • Number of events 8
0.79%
9/1142 • Number of events 9
Respiratory, thoracic and mediastinal disorders
Pulmonary disease/Pneumonia/Bronchitis/Asthma/Breathing difficulties
7.5%
87/1163 • Number of events 133
6.9%
79/1142 • Number of events 100
Respiratory, thoracic and mediastinal disorders
PULMONARY/UPPER RESPIRATORY: Other
0.60%
7/1163 • Number of events 7
0.26%
3/1142 • Number of events 3
Renal and urinary disorders
Acute renal failure/Proteinuria
2.4%
28/1163 • Number of events 32
2.9%
33/1142 • Number of events 36
Renal and urinary disorders
RENAL/GENITOURINARY: Other
0.60%
7/1163 • Number of events 7
0.61%
7/1142 • Number of events 7
Reproductive system and breast disorders
SEXUAL/REPRODUCTIVE FUNCTION: Other
0.17%
2/1163 • Number of events 2
0.53%
6/1142 • Number of events 6
Surgical and medical procedures
"Cardiac device implantation (pacemaker, defibrillator, etc.)"
10.6%
123/1163 • Number of events 133
9.5%
109/1142 • Number of events 118
Surgical and medical procedures
"Cardiac procedure (stent, catheterization, EP study, ablation, etc.)"
5.3%
62/1163 • Number of events 76
5.8%
66/1142 • Number of events 82
Surgical and medical procedures
Cardiac surgery
2.4%
28/1163 • Number of events 28
2.0%
23/1142 • Number of events 25
Surgical and medical procedures
Non-cardiac surgery/Diagnostic surgery
6.4%
75/1163 • Number of events 102
5.0%
57/1142 • Number of events 67
Surgical and medical procedures
SURGERY/INTRA-OPERATIVE INJURY: Other
0.34%
4/1163 • Number of events 4
0.70%
8/1142 • Number of events 8
Vascular disorders
Systemic embolism
0.26%
3/1163 • Number of events 3
0.44%
5/1142 • Number of events 5
Vascular disorders
VASCULAR: Other
1.4%
16/1163 • Number of events 17
1.1%
13/1142 • Number of events 13

Other adverse events

Other adverse events
Measure
Aspirin
n=1163 participants at risk
Aspirin : 325 mg per day
Warfarin
n=1142 participants at risk
Warfarin : INR 2.5-3.0; target INR 2.75
General disorders
All non-serious adverse events
64.4%
749/1163 • Number of events 4483
70.0%
799/1142 • Number of events 4895

Additional Information

Dr. J.L.P. (Seamus) Thompson

Columbia University

Phone: 212-342-1252

Results disclosure agreements

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