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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Shunichi Homma, Columbia University
ClinicalTrials.gov Identifier:
NCT00041938
First received: July 19, 2002
Last updated: April 1, 2013
Last verified: April 2013
Results First Received: January 3, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Prevention
Conditions: Heart Disease
Stroke
Ischemic Heart Disease
Myocardial Infarction
Interventions: Drug: aspirin
Drug: Warfarin

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruited 2305 patients at 176 sites in 11 countries, between 10/1/2002 and 1/31/2010.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Intent-to-treat trial - all randomized patients followed and analyzed.

Reporting Groups
  Description
Aspirin Aspirin : 325 mg per day
Warfarin Warfarin : International Normalized Ratio (INR) 2.5-3.0; target INR 2.75

Participant Flow:   Overall Study
    Aspirin     Warfarin  
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
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Aspirin Aspirin : 325 mg per day
Warfarin Warfarin : INR 2.5-3.0; target INR 2.75
Total Total of all reporting groups

Baseline Measures
    Aspirin     Warfarin     Total  
Number of Participants  
[units: participants]
  1163     1142     2305  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     732     706     1438  
>=65 years     431     436     867  
Age  
[units: years]
Mean ± Standard Deviation
  61  ± 11.1     61  ± 11.6     61  ± 11.3  
Gender, Customized  
[units: participants]
     
Male     936     904     1840  
Female     224     236     460  
Unknown     3     2     5  
Region of Enrollment  
[units: participants]
     
North America     546     573     1119  
Europe     567     527     1094  
Argentina     50     42     92  



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Event Rate Per 100 Patient Years for Composite Endpoint of Ischemic Stroke, Intracerebral Hemorrhage, or Death   [ 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 ]

Measure Type Primary
Measure Title Event Rate Per 100 Patient Years for Composite Endpoint of Ischemic Stroke, Intracerebral Hemorrhage, or Death
Measure 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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat analysis: all enrolled patients were analyzed.

Reporting Groups
  Description
Aspirin Aspirin : 325 mg per day
Warfarin Warfarin : INR 2.5-3.0; target INR 2.75

Measured Values
    Aspirin     Warfarin  
Number of Participants Analyzed  
[units: participants]
  1163     1142  
Event Rate Per 100 Patient Years for Composite Endpoint of Ischemic Stroke, Intracerebral Hemorrhage, or Death  
[units: events per 100 patient-years]
  7.93     7.47  


Statistical Analysis 1 for Event Rate Per 100 Patient Years for Composite Endpoint of Ischemic Stroke, Intracerebral Hemorrhage, or Death
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] 0.40
Hazard Ratio (HR) [4] 0.93
95% Confidence Interval ( 0.79 to 1.10 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  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.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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.
[4] Other relevant estimation information:
  Hazard ratio is for comparison of warfarin vs. aspirin. Warfarin represents the numerator and aspirin represents the denominator of the hazard ratio.



2.  Secondary:   Event Rate Per 100 Patient-years for Composite Endpoint of Hospitalization for Heart Failure, Myocardial Infarction, Ischemic Stroke, Intracerebral Hemorrhage, or Death.   [ 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. ]

Measure Type Secondary
Measure Title Event Rate Per 100 Patient-years for Composite Endpoint of Hospitalization for Heart Failure, Myocardial Infarction, Ischemic Stroke, Intracerebral Hemorrhage, or Death.
Measure 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.  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat analysis: all enrolled patients were analyzed.

Reporting Groups
  Description
Aspirin Aspirin : 325 mg per day
Warfarin Warfarin : INR 2.5-3.0; target INR 2.75

Measured Values
    Aspirin     Warfarin  
Number of Participants Analyzed  
[units: participants]
  1163     1142  
Event Rate Per 100 Patient-years for Composite Endpoint of Hospitalization for Heart Failure, Myocardial Infarction, Ischemic Stroke, Intracerebral Hemorrhage, or Death.  
[units: events per 100 patient-years]
  12.15     12.70  


Statistical Analysis 1 for Event Rate Per 100 Patient-years for Composite Endpoint of Hospitalization for Heart Failure, Myocardial Infarction, Ischemic Stroke, Intracerebral Hemorrhage, or Death.
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] 0.33
Hazard Ratio (HR) [4] 1.07
95% Confidence Interval ( 0.93 to 1.23 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  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.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Secondary null hypothesis was tested at two-tailed alpha = 0.05.
[4] Other relevant estimation information:
  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:   Event Rate Per 100 Patient-years for Ischemic Stroke   [ Time Frame: From date of randomization to date of ischemic stroke component of primary composite outcome, up to 6 years ]

Measure Type Other Pre-specified
Measure Title Event Rate Per 100 Patient-years for Ischemic Stroke
Measure 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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat

Reporting Groups
  Description
Aspirin Aspirin : 325 mg per day
Warfarin Warfarin : INR 2.5-3.0; target INR 2.75

Measured Values
    Aspirin     Warfarin  
Number of Participants Analyzed  
[units: participants]
  1163     1142  
Event Rate Per 100 Patient-years for Ischemic Stroke  
[units: rate per 100 patient years]
  1.36     0.72  


Statistical Analysis 1 for Event Rate Per 100 Patient-years for Ischemic Stroke
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] 0.005
Hazard Ratio (HR) [4] 0.52
95% Confidence Interval ( 0.33 to 0.82 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Null hypothesis: there is no difference between warfarin and aspirin in time to ischemic stroke, adjusting for competing risks of death and intracerebral hemorrhage.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Cause-specific Cox model, stratified by site, NYHA class (I vs. II, III, or IV), and prior stroke or TIA status.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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:   Event Rate Per 100 Patient-years for Intracerebral Hemorrhage   [ Time Frame: From date of randomization to date of intracerebral hemorrhage component of primary composite outcome, up to 6 years ]

Measure Type Other Pre-specified
Measure Title Event Rate Per 100 Patient-years for Intracerebral Hemorrhage
Measure 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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat

Reporting Groups
  Description
Aspirin Aspirin : 325 mg per day
Warfarin Warfarin : INR 2.5-3.0; target INR 2.75

Measured Values
    Aspirin     Warfarin  
Number of Participants Analyzed  
[units: participants]
  1163     1142  
Event Rate Per 100 Patient-years for Intracerebral Hemorrhage  
[units: rate per 100 patient years]
  0.05     0.12  


Statistical Analysis 1 for Event Rate Per 100 Patient-years for Intracerebral Hemorrhage
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] 0.35
Hazard Ratio (HR) [4] 2.22
95% Confidence Interval ( 0.43 to 11.66 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Null hypothesis: there is no difference between warfarin and aspirin in time to intracerebral hemorrhage, adjusting for competing risks of death and ischemic stroke.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Cause-specific Cox model, stratified by site, NYHA class (I vs. II, III, or IV), and prior stroke or TIA status.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



5.  Other Pre-specified:   Event Rate Per 100 Patient-years for Death   [ Time Frame: From date of randomization to date of death component of primary composite outcome, up to 6 years ]

Measure Type Other Pre-specified
Measure Title Event Rate Per 100 Patient-years for Death
Measure 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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat

Reporting Groups
  Description
Aspirin Aspirin : 325 mg per day
Warfarin Warfarin : INR 2.5-3.0; target INR 2.75

Measured Values
    Aspirin     Warfarin  
Number of Participants Analyzed  
[units: participants]
  1163     1142  
Event Rate Per 100 Patient-years for Death  
[units: events per 100 patient-years]
  6.52     6.63  


Statistical Analysis 1 for Event Rate Per 100 Patient-years for Death
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] 0.91
Hazard Ratio (HR) [4] 1.01
95% Confidence Interval ( 0.85 to 1.20 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Cause-specific Cox model, stratified by site, NYHA class (I vs. II, III, or IV), and prior stroke or TIA status.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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:   Event Rate Per 100 Patient Years of Myocardial Infarction Component of Secondary Composite Outcome   [ Time Frame: From date of randomization to date of myocardial infarction component of secondary composite outcome, up to 6 years ]

Measure Type Other Pre-specified
Measure Title Event Rate Per 100 Patient Years of Myocardial Infarction Component of Secondary Composite Outcome
Measure 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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat

Reporting Groups
  Description
Aspirin Aspirin : 325 mg per day
Warfarin Warfarin : INR 2.5-3.0; target INR 2.75

Measured Values
    Aspirin     Warfarin  
Number of Participants Analyzed  
[units: participants]
  1163     1142  
Event Rate Per 100 Patient Years of Myocardial Infarction Component of Secondary Composite Outcome  
[units: events per 100 patient years]
  0.87     0.80  


Statistical Analysis 1 for Event Rate Per 100 Patient Years of Myocardial Infarction Component of Secondary Composite Outcome
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] 0.93
Hazard Ratio (HR) [4] 0.98
95% Confidence Interval ( 0.58 to 1.64 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Cause-specific Cox model, stratified by site, NYHA class (I vs. II, III, or IV), and prior stroke or TIA status.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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:   Event Rate Per 100 Patient Years of Heart Failure Hospitalization Component of Secondary Composite Outcome.   [ Time Frame: From date of randomization to date of heart failure hospitalization component of secondary composite outcome, up to 6 years ]

Measure Type Other Pre-specified
Measure Title Event Rate Per 100 Patient Years of Heart Failure Hospitalization Component of Secondary Composite Outcome.
Measure 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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat.

Reporting Groups
  Description
Aspirin Aspirin : 325 mg per day
Warfarin Warfarin : INR 2.5-3.0; target INR 2.75

Measured Values
    Aspirin     Warfarin  
Number of Participants Analyzed  
[units: participants]
  1163     1142  
Event Rate Per 100 Patient Years of Heart Failure Hospitalization Component of Secondary Composite Outcome.  
[units: events per 100 patient years]
  5.67     6.79  


Statistical Analysis 1 for Event Rate Per 100 Patient Years of Heart Failure Hospitalization Component of Secondary Composite Outcome.
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] 0.053
Hazard Ratio (HR) [4] 1.21
95% Confidence Interval ( 0.998 to 1.47 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Cause-specific Cox model, stratified by site, NYHA class (I vs. II, III, or IV), and prior stroke or TIA status.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



8.  Other Pre-specified:   Event Rate Per 100 Patient Years of Ischemic Stroke Component of Secondary Composite Outcome   [ Time Frame: From date of randomization to date of ischemic stroke component of secondary composite outcome, up to 6 years ]

Measure Type Other Pre-specified
Measure Title Event Rate Per 100 Patient Years of Ischemic Stroke Component of Secondary Composite Outcome
Measure 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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat.

Reporting Groups
  Description
Aspirin Aspirin : 325 mg per day
Warfarin Warfarin : INR 2.5-3.0; target INR 2.75

Measured Values
    Aspirin     Warfarin  
Number of Participants Analyzed  
[units: participants]
  1163     1142  
Event Rate Per 100 Patient Years of Ischemic Stroke Component of Secondary Composite Outcome  
[units: events per 100 patient years]
  1.14     0.57  


Statistical Analysis 1 for Event Rate Per 100 Patient Years of Ischemic Stroke Component of Secondary Composite Outcome
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] 0.03
Hazard Ratio (HR) [4] 0.55
95% Confidence Interval ( 0.32 to 0.96 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Cause-specific Cox model, stratified by site, NYHA class (I vs. II, III, or IV), and prior stroke or TIA status.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



9.  Other Pre-specified:   Event Rate Per 100 Patient Years of Intracerebral Hemorrhage Component of Secondary Composite Outcome   [ Time Frame: From date of randomization to date of intracerebral hemorrhage component of secondary composite outcome, up to 6 years ]

Measure Type Other Pre-specified
Measure Title Event Rate Per 100 Patient Years of Intracerebral Hemorrhage Component of Secondary Composite Outcome
Measure 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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat

Reporting Groups
  Description
Aspirin Aspirin : 325 mg per day
Warfarin Warfarin : INR 2.5-3.0; target INR 2.75

Measured Values
    Aspirin     Warfarin  
Number of Participants Analyzed  
[units: participants]
  1163     1142  
Event Rate Per 100 Patient Years of Intracerebral Hemorrhage Component of Secondary Composite Outcome  
[units: events per 100 patient years]
  0.06     0.11  


Statistical Analysis 1 for Event Rate Per 100 Patient Years of Intracerebral Hemorrhage Component of Secondary Composite Outcome
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] 0.51
Hazard Ratio (HR) [4] 1.77
95% Confidence Interval ( 0.32 to 9.88 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Cause-specific Cox model, stratified by site, NYHA class (I vs. II, III, or IV), and prior stroke or TIA status.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  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:   Event Rate Per 100 Patient Years of Death Component of Secondary Composite Outcome   [ Time Frame: From date of randomization to date of death component of secondary composite outcome, up to 6 years ]

Measure Type Other Pre-specified
Measure Title Event Rate Per 100 Patient Years of Death Component of Secondary Composite Outcome
Measure 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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat

Reporting Groups
  Description
Aspirin Aspirin : 325 mg per day
Warfarin Warfarin : INR 2.5-3.0; target INR 2.75

Measured Values
    Aspirin     Warfarin  
Number of Participants Analyzed  
[units: participants]
  1163     1142  
Event Rate Per 100 Patient Years of Death Component of Secondary Composite Outcome  
[units: events per 100 patient years]
  4.41     4.43  


Statistical Analysis 1 for Event Rate Per 100 Patient Years of Death Component of Secondary Composite Outcome
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] 0.83
Hazard Ratio (HR) [4] 1.03
95% Confidence Interval ( 0.81 to 1.30 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Cause-specific Cox model, stratified by site, NYHA class (I vs. II, III, or IV), and prior stroke or TIA status.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



11.  Other Pre-specified:   Rate Per 100 Patient Years of Major Hemorrhage   [ Time Frame: From date of randomization until end of scheduled follow-up, up to 6 years ]

Measure Type Other Pre-specified
Measure Title Rate Per 100 Patient Years of Major Hemorrhage
Measure 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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat

Reporting Groups
  Description
Aspirin Aspirin : 325 mg per day
Warfarin Warfarin : INR 2.5-3.0; target INR 2.75

Measured Values
    Aspirin     Warfarin  
Number of Participants Analyzed  
[units: participants]
  1163     1142  
Rate Per 100 Patient Years of Major Hemorrhage  
[units: events per 100 patient years]
  0.87     1.78  


Statistical Analysis 1 for Rate Per 100 Patient Years of Major Hemorrhage
Groups [1] All groups
Method [2] Regression, Poisson
P Value [3] <0.001
Rate ratio [4] 2.05
95% Confidence Interval ( 1.36 to 3.12 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  The warfarin arm represents the numerator and the aspirin arm represents the denominator of the rate ratio.



12.  Other Pre-specified:   Rate Per 100 Patient-years of Minor Hemorrhage.   [ Time Frame: From date of randomization until the end of scheduled follow-up, up to 6 years ]

Measure Type Other Pre-specified
Measure Title Rate Per 100 Patient-years of Minor Hemorrhage.
Measure 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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat

Reporting Groups
  Description
Aspirin Aspirin : 325 mg per day
Warfarin Warfarin : INR 2.5-3.0; target INR 2.75

Measured Values
    Aspirin     Warfarin  
Number of Participants Analyzed  
[units: participants]
  1163     1142  
Rate Per 100 Patient-years of Minor Hemorrhage.  
[units: events per 100 patient-years]
  7.34     11.6  


Statistical Analysis 1 for Rate Per 100 Patient-years of Minor Hemorrhage.
Groups [1] All groups
Method [2] Regression, Poisson
P Value [3] <0.001
Rate ratio [4] 1.56
95% Confidence Interval ( 1.34 to 1.81 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  Warfarin group represents the numerator and aspirin group represents denominator of rate ratio.




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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