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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Shunichi Homma, Columbia University
ClinicalTrials.gov Identifier:
NCT00041938
First received: July 19, 2002
Last updated: August 29, 2014
Last verified: August 2014
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
  Hide Baseline Characteristics

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
  Show 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 ]

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. ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]


  Serious Adverse Events
  Hide Serious Adverse Events

Time Frame No text entered.
Additional Description No text entered.

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

Serious Adverse Events
    Aspirin     Warfarin  
Total, serious adverse events      
# participants affected / at risk     617/1163 (53.05%)     632/1142 (55.34%)  
Blood and lymphatic system disorders      
Blood dyscrasia    
# participants affected / at risk     3/1163 (0.26%)     4/1142 (0.35%)  
# events     3     4  
BLOOD/BONE MARROW: Other    
# participants affected / at risk     1/1163 (0.09%)     3/1142 (0.26%)  
# events     1     4  
Thrombocytopenia/Anemia/Leukopenia    
# participants affected / at risk     1/1163 (0.09%)     12/1142 (1.05%)  
# events     1     12  
Hemorrhage/Bleeding    
# participants affected / at risk     0/1163 (0.00%)     1/1142 (0.09%)  
# events     0     1  
LYMPHATICS: Other    
# participants affected / at risk     1/1163 (0.09%)     0/1142 (0.00%)  
# events     1     0  
Peripheral edema    
# participants affected / at risk     4/1163 (0.34%)     4/1142 (0.35%)  
# events     4     4  
Cardiac disorders      
Atrial fibrillation/Atrial flutter/Supraventricular tachycardia    
# participants affected / at risk     56/1163 (4.82%)     35/1142 (3.06%)  
# events     67     45  
Bradycardia    
# participants affected / at risk     6/1163 (0.52%)     6/1142 (0.53%)  
# events     6     6  
CARDIAC ARRHYTHMIA: Other    
# participants affected / at risk     7/1163 (0.60%)     3/1142 (0.26%)  
# events     7     3  
Ventricular fibrillation    
# participants affected / at risk     7/1163 (0.60%)     15/1142 (1.31%)  
# events     8     17  
Ventricular tachycardia    
# participants affected / at risk     24/1163 (2.06%)     39/1142 (3.42%)  
# events     33     46  
Acute cardiac failure/CHF/Pulmonary edema    
# participants affected / at risk     209/1163 (17.97%)     243/1142 (21.28%)  
# events     432     506  
AICD firing/discharge    
# participants affected / at risk     16/1163 (1.38%)     20/1142 (1.75%)  
# events     21     21  
Angina/Chest pain    
# participants affected / at risk     70/1163 (6.02%)     88/1142 (7.71%)  
# events     105     148  
CARDIAC GENERAL: Other    
# participants affected / at risk     16/1163 (1.38%)     16/1142 (1.40%)  
# events     18     19  
Malignant hypertension    
# participants affected / at risk     3/1163 (0.26%)     7/1142 (0.61%)  
# events     3     7  
Myocardial infarction/Acute Coronary Syndrome    
# participants affected / at risk     48/1163 (4.13%)     50/1142 (4.38%)  
# events     60     59  
Pulmonary embolism    
# participants affected / at risk     6/1163 (0.52%)     5/1142 (0.44%)  
# events     6     5  
Endocrine disorders      
Diabetes mellitus and its complications    
# participants affected / at risk     26/1163 (2.24%)     22/1142 (1.93%)  
# events     35     35  
ENDOCRINE: Other    
# participants affected / at risk     2/1163 (0.17%)     1/1142 (0.09%)  
# events     2     1  
Eye disorders      
OCULAR/VISUAL: Other    
# participants affected / at risk     5/1163 (0.43%)     3/1142 (0.26%)  
# events     7     5  
Gastrointestinal disorders      
Gastrointestinal disturbance/Diarrhea/Jaundice/Nausea/Stomach pain/Etc.    
# participants affected / at risk     54/1163 (4.64%)     66/1142 (5.78%)  
# events     70     82  
GASTROINTESTINAL: Other    
# participants affected / at risk     25/1163 (2.15%)     17/1142 (1.49%)  
# events     31     18  
General disorders      
ALLERGY/IMMUNOLOGY: Other    
# participants affected / at risk     1/1163 (0.09%)     1/1142 (0.09%)  
# events     1     1  
Laryngeal edema/Allergic reaction/Anaphylaxis/Angioedema/Rash    
# participants affected / at risk     4/1163 (0.34%)     2/1142 (0.18%)  
# events     4     2  
CONSTITUTIONAL SYMPTOMS: Other    
# participants affected / at risk     7/1163 (0.60%)     1/1142 (0.09%)  
# events     7     1  
Drug abuse    
# participants affected / at risk     3/1163 (0.26%)     1/1142 (0.09%)  
# events     3     1  
OTHER: Other    
# participants affected / at risk     19/1163 (1.63%)     32/1142 (2.80%)  
# events     23     33  
Pregnancy    
# participants affected / at risk     0/1163 (0.00%)     1/1142 (0.09%)  
# events     0     1  
Suicide attempt/Psychiatric disorder    
# participants affected / at risk     16/1163 (1.38%)     10/1142 (0.88%)  
# events     16     10  
PAIN: Other    
# participants affected / at risk     14/1163 (1.20%)     13/1142 (1.14%)  
# events     15     20  
Hepatobiliary disorders      
Acute hepatic failure    
# participants affected / at risk     3/1163 (0.26%)     3/1142 (0.26%)  
# events     3     3  
HEPATOBILIARY/PANCREAS: Other    
# participants affected / at risk     3/1163 (0.26%)     5/1142 (0.44%)  
# events     3     7  
Infections and infestations      
Infection/Sepsis/Fever    
# participants affected / at risk     66/1163 (5.67%)     79/1142 (6.92%)  
# events     79     97  
Metabolism and nutrition disorders      
Metabolic disturbance/Gout    
# participants affected / at risk     14/1163 (1.20%)     16/1142 (1.40%)  
# events     15     17  
METABOLIC/LABORATORY: Other    
# participants affected / at risk     12/1163 (1.03%)     10/1142 (0.88%)  
# events     14     11  
Musculoskeletal and connective tissue disorders      
MUSCULOSKELETAL/SOFT TISSUE: Other    
# participants affected / at risk     39/1163 (3.35%)     29/1142 (2.54%)  
# events     43     32  
Visceral necrosis    
# participants affected / at risk     0/1163 (0.00%)     4/1142 (0.35%)  
# events     0     4  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
MALIGNANCY: Other    
# participants affected / at risk     22/1163 (1.89%)     20/1142 (1.75%)  
# events     24     24  
Nervous system disorders      
Convulsions/Seizures    
# participants affected / at risk     6/1163 (0.52%)     5/1142 (0.44%)  
# events     6     10  
NEUROLOGY: Other    
# participants affected / at risk     8/1163 (0.69%)     7/1142 (0.61%)  
# events     8     7  
Stroke or TIA    
# participants affected / at risk     13/1163 (1.12%)     15/1142 (1.31%)  
# events     16     16  
Syncope/Pre-syncope    
# participants affected / at risk     41/1163 (3.53%)     68/1142 (5.95%)  
# events     48     83  
Renal and urinary disorders      
Acute renal failure/Proteinuria    
# participants affected / at risk     28/1163 (2.41%)     33/1142 (2.89%)  
# events     32     36  
RENAL/GENITOURINARY: Other    
# participants affected / at risk     7/1163 (0.60%)     7/1142 (0.61%)  
# events     7     7  
Reproductive system and breast disorders      
SEXUAL/REPRODUCTIVE FUNCTION: Other    
# participants affected / at risk     2/1163 (0.17%)     6/1142 (0.53%)  
# events     2     6  
Respiratory, thoracic and mediastinal disorders      
Acute respiratory failure    
# participants affected / at risk     7/1163 (0.60%)     9/1142 (0.79%)  
# events     8     9  
Pulmonary disease/Pneumonia/Bronchitis/Asthma/Breathing difficulties    
# participants affected / at risk     87/1163 (7.48%)     79/1142 (6.92%)  
# events     133     100  
PULMONARY/UPPER RESPIRATORY: Other    
# participants affected / at risk     7/1163 (0.60%)     3/1142 (0.26%)  
# events     7     3  
Skin and subcutaneous tissue disorders      
DERMATOLOGY/SKIN: Other    
# participants affected / at risk     1/1163 (0.09%)     0/1142 (0.00%)  
# events     1     0  
Grade 4 dermatologic manifestations    
# participants affected / at risk     1/1163 (0.09%)     1/1142 (0.09%)  
# events     2     1  
Surgical and medical procedures      
"Cardiac device implantation (pacemaker, defibrillator, etc.)"    
# participants affected / at risk     123/1163 (10.58%)     109/1142 (9.54%)  
# events     133     118  
"Cardiac procedure (stent, catheterization, EP study, ablation, etc.)"    
# participants affected / at risk     62/1163 (5.33%)     66/1142 (5.78%)  
# events     76     82  
Cardiac surgery    
# participants affected / at risk     28/1163 (2.41%)     23/1142 (2.01%)  
# events     28     25  
Non-cardiac surgery/Diagnostic surgery    
# participants affected / at risk     75/1163 (6.45%)     57/1142 (4.99%)  
# events     102     67  
SURGERY/INTRA-OPERATIVE INJURY: Other    
# participants affected / at risk     4/1163 (0.34%)     8/1142 (0.70%)  
# events     4     8  
Vascular disorders      
Systemic embolism    
# participants affected / at risk     3/1163 (0.26%)     5/1142 (0.44%)  
# events     3     5  
VASCULAR: Other    
# participants affected / at risk     16/1163 (1.38%)     13/1142 (1.14%)  
# events     17     13  
Events were collected by systematic assessment




  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
No text entered.


  More Information
  Hide 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.


Results Point of Contact:  
Name/Title: Dr. J.L.P. (Seamus) Thompson
Organization: Columbia University
phone: 212-342-1252
e-mail: jlt12@columbia.edu


No publications provided by Columbia University

Publications automatically indexed to this study:

Responsible Party: Shunichi Homma, Columbia University
ClinicalTrials.gov Identifier: NCT00041938     History of Changes
Other Study ID Numbers: AAAC1093, U01NS039143-01, R01NS39154, CRC
Study First Received: July 19, 2002
Results First Received: January 3, 2013
Last Updated: August 29, 2014
Health Authority: United States: Federal Government