Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial
WARCEF
4 other identifiers
interventional
2,305
2 countries
64
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Oct 2002
Longer than P75 for phase_3
64 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 19, 2002
CompletedFirst Posted
Study publicly available on registry
July 22, 2002
CompletedStudy Start
First participant enrolled
October 1, 2002
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2011
CompletedResults Posted
Study results publicly available
May 14, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2014
CompletedSeptember 5, 2014
August 1, 2014
8.8 years
July 19, 2002
January 3, 2013
August 29, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
From date of randomization until the date of the first to occur of ischemic stroke, intracerebral hemorrhage, or death, up to 6 years
Secondary Outcomes (1)
Event Rate Per 100 Patient-years for Composite Endpoint of Hospitalization for Heart Failure, Myocardial Infarction, Ischemic Stroke, Intracerebral Hemorrhage, or Death.
From randomization to the first to occur of hospitalization for heart failure, myocardial infarction, ischemic stroke, intracerebral hemorrhage, or death, up to a maximum of 6 years.
Other Outcomes (10)
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
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
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
- +7 more other outcomes
Study Arms (2)
aspirin
ACTIVE COMPARATORAspirin: 325 mg per day
warfarin
ACTIVE COMPARATORWarfarin: International Normalized Ratio (INR) 2.5-3.0; target INR 2.75
Interventions
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (64)
Southern Arizona Veterans Affairs Medical Center
Tucson, Arizona, United States
University of Arizona Health Sciences Center
Tucson, Arizona, United States
Santa Clara Medical Center
Santa Clara, California, United States
West Los Angeles Veterans Affairs Medical Center
West Los Angeles, California, United States
Denver Health Medical Center
Denver, Colorado, United States
Denver Veterans Affairs Medical Center
Denver, Colorado, United States
George Washington University
Washington D.C., District of Columbia, 20037, United States
Mayo Clinic Transplant Center
Jacksonville, Florida, United States
Melbourne Internal Medicine Associates
Melbourne, Florida, United States
Jackson Memorial Hospital/U. of Miami
Miami, Florida, United States
Mercy Research Institute
Miami, Florida, United States
Cardiovascular Consultants of South Florida
Tamarac, Florida, United States
Morehouse School of Medicine
Atlanta, Georgia, United States
Northeast Georgia Heart Center
Gainesville, Georgia, United States
University of Illinois at Chicago
Chicago, Illinois, United States
Methodist Heart, Lung and Vascular Institute
Peoria, Illinois, United States
University of Kentucky
Lexington, Kentucky, United States
Louisville Veterans Affairs Medical Center
Louisville, Kentucky, United States
University of Louisville
Louisville, Kentucky, United States
Gulf Regional Research, LLC
Metairie, Louisiana, United States
LSU Health Sciences Center
Shreveport, Louisiana, United States
Lahey Clinic
Burlington, Massachusetts, United States
Veterans Affairs Medical Center
Detroit, Michigan, United States
Mercy Health Partners
Muskegon, Michigan, United States
Reno Veterans Affairs Medical Center
Reno, Nevada, United States
Concord Hospital
Concord, New Hampshire, United States
UMDNJ - New Brunswick
New Brunswick, New Jersey, United States
University of Medicine and Dentistry of New Jersey
Newark, New Jersey, United States
Albany Medical College
Albany, New York, United States
Buffalo General Hospital
Buffalo, New York, United States
Kaleida Health Millard Fillmore Hospital
Buffalo, New York, United States
Five Towns Neuroscience Research
Cedarhurst, New York, United States
Long Island Jewish Medical Center
New Hyde Park, New York, United States
Columbia University, New York Presbyterian Hospital PH 3-342
New York, New York, 10032, United States
Columbia University Medical Center
New York, New York, United States
Mount Sinai Medical Center
New York, New York, United States
Northport Veterans Affairs Medical Center
Northport, New York, United States
University of Rochester Medical Center
Rochester, New York, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
MetroHealth Medical Center
Cleveland, Ohio, United States
Oklahoma City Veterans Affairs Medical Center
Oklahoma City, Oklahoma, United States
Lehigh Valley Hospital
Allentown, Pennsylvania, United States
Tri-State Medical Group Cardiology
Beaver, Pennsylvania, United States
Sewickley Valley Medical Group, Cardiology
Leetsdale, Pennsylvania, United States
Albert Einstein Medical Center
Philadelphia, Pennsylvania, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
Penn Presbyterian Medical Center
Philadelphia, Pennsylvania, United States
Temple University Hospital
Philadelphia, Pennsylvania, United States
Black Hills Health Care System
Fort Meade, South Dakota, United States
Brooke Army Medical Center MCHE - MDC Cardiology Service
Fort Sam Houston, Texas, United States
Michael E. DeBakey Veterans Affairs Medical Center-MEDVAMC
Houston, Texas, United States
Salem VAMC
Salem, Virginia, United States
Huntington Veterans Affairs Medical Center
Huntington, West Virginia, United States
William S. Middleton Memorial Veterans Hospital
Madison, Wisconsin, United States
Center for Neurologic Research
Lethbridge, Alberta, Canada
St. Boniface General Hospital
Winnipeg, Manitoba, Canada
Saint John Regional Hospital
Saint John, New Brunswick, Canada
QE II Health Sciences Centre
Halifax, Nova Scotia, Canada
London Health Sciences Centre
London, Ontario, Canada
Ottawa Heart Institute
Ottawa, Ontario, Canada
Etobicoke Cardiac Research Centre
Rexdale, Ontario, Canada
St. Michael's Hospital
Toronto, Ontario, Canada
Montreal General Hospital
Montreal, Quebec, Canada
Montreal Heart Institute
Montreal, Quebec, Canada
Related Publications (9)
Corica B, Romiti GF, Simoni AH, Mei DA, Bucci T, Thompson JLP, Qian M, Homma S, Proietti M, Lip GYH; WARCEF Investigators. Educational status affects prognosis of patients with heart failure with reduced ejection fraction: A post-hoc analysis from the WARCEF trial. Eur J Clin Invest. 2024 May;54(5):e14152. doi: 10.1111/eci.14152. Epub 2024 Jan 11.
PMID: 38205865DERIVEDLee TC, Qian M, Liu Y, Graham S, Mann DL, Nakanishi K, Teerlink JR, Lip GYH, Freudenberger RS, Sacco RL, Mohr JP, Labovitz AJ, Ponikowski P, Lok DJ, Matsumoto K, Estol C, Anker SD, Pullicino PM, Buchsbaum R, Levin B, Thompson JLP, Homma S, Di Tullio MR; WARCEF Investigators. Cognitive Decline Over Time in Patients With Systolic Heart Failure: Insights From WARCEF. JACC Heart Fail. 2019 Dec;7(12):1042-1053. doi: 10.1016/j.jchf.2019.09.003.
PMID: 31779926DERIVEDTeerlink JR, Qian M, Bello NA, Freudenberger RS, Levin B, Di Tullio MR, Graham S, Mann DL, Sacco RL, Mohr JP, Lip GYH, Labovitz AJ, Lee SC, Ponikowski P, Lok DJ, Anker SD, Thompson JLP, Homma S; WARCEF Investigators. Aspirin Does Not Increase Heart Failure Events in Heart Failure Patients: From the WARCEF Trial. JACC Heart Fail. 2017 Aug;5(8):603-610. doi: 10.1016/j.jchf.2017.04.011.
PMID: 28774396DERIVEDDi Tullio MR, Qian M, Thompson JL, Labovitz AJ, Mann DL, Sacco RL, Pullicino PM, Freudenberger RS, Teerlink JR, Graham S, Lip GY, Levin B, Mohr JP, Buchsbaum R, Estol CJ, Lok DJ, Ponikowski P, Anker SD, Homma S; WARCEF Investigators. Left Ventricular Ejection Fraction and Risk of Stroke and Cardiac Events in Heart Failure: Data From the Warfarin Versus Aspirin in Reduced Ejection Fraction Trial. Stroke. 2016 Aug;47(8):2031-7. doi: 10.1161/STROKEAHA.116.013679. Epub 2016 Jun 28.
PMID: 27354224DERIVEDFreudenberger RS, Cheng B, Mann DL, Thompson JL, Sacco RL, Buchsbaum R, Sanford A, Pullicino PM, Levin B, Teerlink JR, Graham S, Mohr JP, Labovitz AJ, Di Tullio MR, Lip GY, Estol CJ, Lok DJ, Ponikowski P, Anker SD, Homma S; WARCEF Investigators. The first prognostic model for stroke and death in patients with systolic heart failure. J Cardiol. 2016 Aug;68(2):100-3. doi: 10.1016/j.jjcc.2015.09.014. Epub 2015 Nov 6.
PMID: 26549533DERIVEDHomma S, Thompson JL, Qian M, Ye S, Di Tullio MR, Lip GY, Mann DL, Sacco RL, Levin B, Pullicino PM, Freudenberger RS, Teerlink JR, Graham S, Mohr JP, Labovitz AJ, Buchsbaum R, Estol CJ, Lok DJ, Ponikowski P, Anker SD; WARCEF Investigators. Quality of anticoagulation control in preventing adverse events in patients with heart failure in sinus rhythm: Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial substudy. Circ Heart Fail. 2015 May;8(3):504-9. doi: 10.1161/CIRCHEARTFAILURE.114.001725. Epub 2015 Apr 7.
PMID: 25850425DERIVEDShaffer JA, Thompson JL, Cheng B, Ye S, Lip GY, Mann DL, Sacco RL, Pullicino PM, Freudenberger RS, Graham S, Mohr JP, Labovitz AJ, Estol CJ, Lok DJ, Ponikowski P, Anker SD, Di Tullio MR, Homma S; WARCEF Investigators. Association of quality of life with anticoagulant control in patients with heart failure: the Warfarin and Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial. Int J Cardiol. 2014 Dec 15;177(2):715-7. doi: 10.1016/j.ijcard.2014.10.012. No abstract available.
PMID: 25456692DERIVEDHomma S, Thompson JL, Sanford AR, Mann DL, Sacco RL, Levin B, Pullicino PM, Freudenberger RS, Teerlink JR, Graham S, Mohr JP, Massie BM, Labovitz AJ, Di Tullio MR, Gabriel AP, Lip GY, Estol CJ, Lok DJ, Ponikowski P, Anker SD; WARCEF Investigators. Benefit of warfarin compared with aspirin in patients with heart failure in sinus rhythm: a subgroup analysis of WARCEF, a randomized controlled trial. Circ Heart Fail. 2013 Sep 1;6(5):988-97. doi: 10.1161/CIRCHEARTFAILURE.113.000372. Epub 2013 Jul 23.
PMID: 23881846DERIVEDHomma S, Thompson JL, Pullicino PM, Levin B, Freudenberger RS, Teerlink JR, Ammon SE, Graham S, Sacco RL, Mann DL, Mohr JP, Massie BM, Labovitz AJ, Anker SD, Lok DJ, Ponikowski P, Estol CJ, Lip GY, Di Tullio MR, Sanford AR, Mejia V, Gabriel AP, del Valle ML, Buchsbaum R; WARCEF Investigators. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med. 2012 May 17;366(20):1859-69. doi: 10.1056/NEJMoa1202299. Epub 2012 May 2.
PMID: 22551105DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. J.L.P. (Seamus) Thompson
- Organization
- Columbia University
Study Officials
- PRINCIPAL INVESTIGATOR
Shunichi Homma, M.D.
Principal Cardiologist, Associate Chief, Division of Cardiology, and Director, Echocardiography Laboratories Professor of Medicine
- PRINCIPAL INVESTIGATOR
Seamus Thompson, PhD
Statistical PI: Clinical Professor of Biostatistics and Neurology
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Margaret Milliken Hatch Professor of Medicine at the New York-Presbyterian Hospital at the Columbia University Medical Center (In Biomedical Engineering)
Study Record Dates
First Submitted
July 19, 2002
First Posted
July 22, 2002
Study Start
October 1, 2002
Primary Completion
August 1, 2011
Study Completion
July 1, 2014
Last Updated
September 5, 2014
Results First Posted
May 14, 2013
Record last verified: 2014-08