Heart Disease, Ischemic Heart Disease, Myocardial Infarction, Stroke
Conditions
Keywords
heart disease, stroke, ischemic heart disease, myocardial infarction, atrial fibrillation, low ejection fraction, cardiac failure, aspirin, Warfarin, anticoagulant
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
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.
Interventions
DRUGaspirin
325 mg per day
DRUGWarfarin
INR 2.5-3.0; target INR 2.75
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Canada, United States
Participant flow
Recruitment details
Recruited 2305 patients at 176 sites in 11 countries, between 10/1/2002 and 1/31/2010.
Pre-assignment details
Intent-to-treat trial - all randomized patients followed and analyzed.
Participants by arm
| Arm | Count |
|---|---|
| Aspirin Aspirin : 325 mg per day | 1,163 |
| Warfarin Warfarin : INR 2.5-3.0; target INR 2.75 | 1,142 |
| Total | 2,305 |
Baseline characteristics
| Characteristic | Aspirin | Warfarin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 431 Participants | 436 Participants | 867 Participants |
| Age, Categorical Between 18 and 65 years | 732 Participants | 706 Participants | 1438 Participants |
| Age, Continuous | 61 years STANDARD_DEVIATION 11.1 | 61 years STANDARD_DEVIATION 11.6 | 61 years STANDARD_DEVIATION 11.3 |
| Region of Enrollment Argentina | 50 participants | 42 participants | 92 participants |
| Region of Enrollment Europe | 567 participants | 527 participants | 1094 participants |
| Region of Enrollment North America | 546 participants | 573 participants | 1119 participants |
| Sex/Gender, Customized Female | 224 participants | 236 participants | 460 participants |
| Sex/Gender, Customized Male | 936 participants | 904 participants | 1840 participants |
| Sex/Gender, Customized Unknown | 3 participants | 2 participants | 5 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 749 / 1,163 | 799 / 1,142 |
| serious Total, serious adverse events | 617 / 1,163 | 632 / 1,142 |
Outcome results
Primary
Event Rate Per 100 Patient Years for Composite Endpoint of Ischemic Stroke, Intracerebral Hemorrhage, or Death
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
Population: Intent-to-treat analysis: all enrolled patients were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aspirin | Event Rate Per 100 Patient Years for Composite Endpoint of Ischemic Stroke, Intracerebral Hemorrhage, or Death | 7.93 events per 100 patient-years |
| Warfarin | Event Rate Per 100 Patient Years for Composite Endpoint of Ischemic Stroke, Intracerebral Hemorrhage, or Death | 7.47 events per 100 patient-years |
Comparison: 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.p-value: 0.495% CI: [0.79, 1.1]Regression, Cox
Secondary
Event Rate Per 100 Patient-years for Composite Endpoint of Hospitalization for Heart Failure, Myocardial Infarction, Ischemic Stroke, Intracerebral Hemorrhage, or Death.
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.
Population: Intent-to-treat analysis: all enrolled patients were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aspirin | 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 |
| Warfarin | Event Rate Per 100 Patient-years for Composite Endpoint of Hospitalization for Heart Failure, Myocardial Infarction, Ischemic Stroke, Intracerebral Hemorrhage, or Death. | 12.70 events per 100 patient-years |
Comparison: 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.p-value: 0.3395% CI: [0.93, 1.23]Regression, Cox
Other Pre-specified
Event Rate Per 100 Patient-years for Death
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
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aspirin | Event Rate Per 100 Patient-years for Death | 6.52 events per 100 patient-years |
| Warfarin | Event Rate Per 100 Patient-years for Death | 6.63 events per 100 patient-years |
p-value: 0.9195% CI: [0.85, 1.2]Regression, Cox
Other Pre-specified
Event Rate Per 100 Patient-years for Intracerebral Hemorrhage
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
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aspirin | Event Rate Per 100 Patient-years for Intracerebral Hemorrhage | 0.05 rate per 100 patient years |
| Warfarin | Event Rate Per 100 Patient-years for Intracerebral Hemorrhage | 0.12 rate per 100 patient years |
Comparison: Null hypothesis: there is no difference between warfarin and aspirin in time to intracerebral hemorrhage, adjusting for competing risks of death and ischemic stroke.p-value: 0.3595% CI: [0.43, 11.66]Regression, Cox
Other Pre-specified
Event Rate Per 100 Patient-years for Ischemic Stroke
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
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aspirin | Event Rate Per 100 Patient-years for Ischemic Stroke | 1.36 rate per 100 patient years |
| Warfarin | Event Rate Per 100 Patient-years for Ischemic Stroke | 0.72 rate per 100 patient years |
Comparison: Null hypothesis: there is no difference between warfarin and aspirin in time to ischemic stroke, adjusting for competing risks of death and intracerebral hemorrhage.p-value: 0.00595% CI: [0.33, 0.82]Regression, Cox
Other Pre-specified
Event Rate Per 100 Patient Years of Death Component of Secondary Composite Outcome
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
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aspirin | Event Rate Per 100 Patient Years of Death Component of Secondary Composite Outcome | 4.41 events per 100 patient years |
| Warfarin | Event Rate Per 100 Patient Years of Death Component of Secondary Composite Outcome | 4.43 events per 100 patient years |
p-value: 0.8395% CI: [0.81, 1.3]Regression, Cox
Other Pre-specified
Event Rate Per 100 Patient Years of Heart Failure Hospitalization Component of Secondary Composite Outcome.
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
Population: Intent-to-treat.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aspirin | Event Rate Per 100 Patient Years of Heart Failure Hospitalization Component of Secondary Composite Outcome. | 5.67 events per 100 patient years |
| Warfarin | Event Rate Per 100 Patient Years of Heart Failure Hospitalization Component of Secondary Composite Outcome. | 6.79 events per 100 patient years |
Comparison: 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.p-value: 0.05395% CI: [0.998, 1.47]Regression, Cox
Other Pre-specified
Event Rate Per 100 Patient Years of Intracerebral Hemorrhage Component of Secondary Composite Outcome
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
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aspirin | Event Rate Per 100 Patient Years of Intracerebral Hemorrhage Component of Secondary Composite Outcome | 0.06 events per 100 patient years |
| Warfarin | Event Rate Per 100 Patient Years of Intracerebral Hemorrhage Component of Secondary Composite Outcome | 0.11 events per 100 patient years |
Comparison: 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.p-value: 0.5195% CI: [0.32, 9.88]Regression, Cox
Other Pre-specified
Event Rate Per 100 Patient Years of Ischemic Stroke Component of Secondary Composite Outcome
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
Population: Intent-to-treat.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aspirin | Event Rate Per 100 Patient Years of Ischemic Stroke Component of Secondary Composite Outcome | 1.14 events per 100 patient years |
| Warfarin | Event Rate Per 100 Patient Years of Ischemic Stroke Component of Secondary Composite Outcome | 0.57 events per 100 patient years |
Comparison: 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.p-value: 0.0395% CI: [0.32, 0.96]Regression, Cox
Other Pre-specified
Event Rate Per 100 Patient Years of Myocardial Infarction Component of Secondary Composite Outcome
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
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aspirin | Event Rate Per 100 Patient Years of Myocardial Infarction Component of Secondary Composite Outcome | 0.87 events per 100 patient years |
| Warfarin | Event Rate Per 100 Patient Years of Myocardial Infarction Component of Secondary Composite Outcome | 0.80 events per 100 patient years |
Comparison: 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.p-value: 0.9395% CI: [0.58, 1.64]Regression, Cox
Other Pre-specified
Rate Per 100 Patient Years of Major Hemorrhage
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
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aspirin | Rate Per 100 Patient Years of Major Hemorrhage | 0.87 events per 100 patient years |
| Warfarin | Rate Per 100 Patient Years of Major Hemorrhage | 1.78 events per 100 patient years |
p-value: <0.00195% CI: [1.36, 3.12]Regression, Poisson
Other Pre-specified
Rate Per 100 Patient-years of Minor Hemorrhage.
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
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aspirin | Rate Per 100 Patient-years of Minor Hemorrhage. | 7.34 events per 100 patient-years |
| Warfarin | Rate Per 100 Patient-years of Minor Hemorrhage. | 11.6 events per 100 patient-years |
p-value: <0.00195% CI: [1.34, 1.81]Regression, Poisson