Warfarin and Antiplatelet Therapy in Chronic Heart Failure
- Conditions
- Heart Failure
- Interventions
- Registration Number
- NCT00007683
- Lead Sponsor
- US Department of Veterans Affairs
- Brief Summary
Whether patients with chronic heart failure (CHF) should be anticoagulated is one of the oldest unresolved questions in cardiovascular therapeutics. Some authorities do not recommend anticoagulation for CHF patients in sinus rhythm, others recommend anticoagulation in patients with primary cardiomyopathy, and still others consider it more appropriate in patients with coronary artery disease (CAD). This absence of consensus reflects the lack of evidence in this area and different outlooks on the objectives of such therapy (e.g., prevention of arterial emboli or reduction in vascular events).
- Detailed Description
Primary Hypothesis: The hypothesis to be tested is whether aspirin, warfarin, and clopidogrel are equally effective in the treatment of patients with symptomatic CHF and reduced ejection fraction.
Secondary Hypothesis: If one therapy proves to be superior with regard to outcomes, what is the cost of this benefit? Can subsets of patients be identified who benefit more from a specific approach to antithrombotic therapy?
Intervention: The three treatment regimens are:
1. Open-label Warfarin titrated to an INR of 2.5-3.0;
2. Double blind aspirin 162 mg once daily;
3. Double blind clopidogrel 75 mg once daily.
Primary Outcomes: Any death (all causes), non-fatal stroke, non-fatal MI.
Study Abstract: Whether patients with chronic heart failure (CHF) should be anticoagulated is one of the oldest unresolved questions in cardiovascular therapeutics. Some authorities do not recommend anticoagulation for CHF patients in sinus rhythm, others recommend anticoagulation in patients with primary cardiomyopathy, and still others consider it more appropriate in patients with coronary artery disease (CAD). This absence of consensus reflects the lack of evidence in this area and different outlooks on the objectives of such therapy (e.g., prevention of arterial emboli or reduction in vascular events).
The original target sample size was 4,500 over a 3 year enrollment period with a 2 year follow-up. This sample size yielded 90% power to detect a relative difference of 20% between treatment groups. The sample size was later amended to 1,500 over a 30 month enrollment period with a 12 month follow-up. The reduced sample size yielded 85% to detect a between treatment difference of 30%. This change became effective in March 2002.
This clinical trial enrolled 1,587 patients in 142 medical centers; VA and non-VA centers in the U.S., and medical centers in the United Kingdom and Canada. Patients were randomly and equally allocated to the 3 treatments: warfarin (administered open-label), aspirin and clopidogrel (the latter two administered double-blind). The study was conducted over a 3.5 year period, with a 2.5 year enrollment phase.
Patients with NYHA class II, III, or IV and left ventricular ejection fractions less than or equal to 35% on an ACE inhibitor (unless not tolerated) and a diuretic were entered. The primary end point is the composite of death from any cause, non-fatal MI, and non-fatal stroke. All-cause mortality is the secondary end point.
The WATCH design paper has been published in the Journal of Cardiac Failure. Preliminary results were presented at the meeting of the American College of Cardiology in New Orleans on March 9, 2004. There were no significant differences between the treatment groups for the primary endpoints. The paper with final results is being prepared.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1587
Inclusion Criteria:
- Patients with NYHA class II, III, or IV and left ventricular ejection fractions less than or equal to 35%, on an ACE inhibitor (unless not tolerated) and on a diuretic.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 Warfarin titrated to an INR of 2.5-3.0 Warfarin Titrated to an INR of 2.5-3.0 3 Clopidogrel 75 Clopidogrel 75 mg 2 Aspirin Aspirin 182 mg
- Primary Outcome Measures
Name Time Method acomposite of mortality, nonfatal myocardial infarction and nonfatal stroke 30 months intake; 12-42 months follow-up The primary safety end point was major bleeding episodes, defined as bleeding episodes leading to death or disability (including loss of neurological or special senses function), requiring surgical intervention, or associated with an acute decline of hemoglobin 2gm/dl or transfusion of \>1 U packed red cells or whole blood.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (134)
Scunthorpe General Hospital
🇬🇧Scunthorpe, North Lincolnshire, United Kingdom
Alder Medical Centre
🇨🇦Campbell River, British Columbia, Canada
Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock
🇺🇸No. Little Rock, Arkansas, United States
VA Medical Center, Memphis
🇺🇸Memphis, Tennessee, United States
VA Gulf Coast Veterans Health Care System, Biloxi
🇺🇸Biloxi, Mississippi, United States
VA Medical Center, Huntington
🇺🇸Huntington, West Virginia, United States
Lincoln Division VA Nebraska Western IA HCS
🇺🇸Lincoln, Nebraska, United States
VA Black Hills Health Care System, Fort Meade
🇺🇸Fort Meade, South Dakota, United States
Cardiology Clinic - Maisonneuve-Rosemont
🇨🇦Montreal, Quebec, Canada
St. Paul's Hospital
🇨🇦Saskatoon, Saskatchewan, Canada
Selly Oak Hospital
🇬🇧Selly Oak, Birmingham, United Kingdom
North Shore University Hospital
🇺🇸Manhasset, New York, United States
VA Medical Center, Loma Linda
🇺🇸Loma Linda, California, United States
VA Medical Center, Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
VA Sierra Nevada Health Care System
🇺🇸Reno, Nevada, United States
Toronto Western Hospital
🇨🇦Toronto, Ontario, Canada
Michael E. DeBakey VA Medical Center (152)
🇺🇸Houston, Texas, United States
St. Boniface General Hospital
🇨🇦Winnipeg, Manitoba, Canada
Wythenshawe Hospital
🇬🇧Wythenshawe, Manchester, United Kingdom
King Geroge Hospital
🇬🇧Ilford, Essex, United Kingdom
VA Medical Center, Fargo
🇺🇸Fargo, North Dakota, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Carl T. Hayden VA Medical Center
🇺🇸Phoenix, Arizona, United States
VA Medical Center, San Francisco
🇺🇸San Francisco, California, United States
VA Medical Center, Miami
🇺🇸Miami, Florida, United States
VA Medical Center, Cincinnati
🇺🇸Cincinnati, Ohio, United States
VA Medical Center
🇺🇸Nashville, Tennessee, United States
VA Salt Lake City Health Care System, Salt Lake City
🇺🇸Salt Lake City, Utah, United States
John D. Dingell VA Medical Center, Detroit
🇺🇸Detroit, Michigan, United States
VA Eastern Colorado Health Care System, Denver
🇺🇸Denver, Colorado, United States
Margaret Pardee Memorial Hospital
🇺🇸Hendersonville, North Carolina, United States
VA Stratton Medical Center, Albany
🇺🇸Albany, New York, United States
James A. Haley Veterans Hospital, Tampa
🇺🇸Tampa, Florida, United States
Cardiovascular Consultants, Walnut Creek
🇺🇸Walnut Creek, California, United States
VA Greater Los Angeles Healthcare System, West LA
🇺🇸West Los Angeles, California, United States
Health Sciences Centre - Cardiology Research
🇨🇦Winnipeg, Manitoba, Canada
VA Medical Center, Birmingham
🇺🇸Birmingham, Alabama, United States
VA Central California Health Care System, Fresno
🇺🇸Fresno, California, United States
VA Medical Center, Syracuse
🇺🇸Syracuse, New York, United States
VA Medical Center, Minneapolis
🇺🇸Minneapolis, Minnesota, United States
VA Medical Center, Durham
🇺🇸Durham, North Carolina, United States
Chalmers P. Wylie VAOPC
🇺🇸Columbus, Ohio, United States
VA Medical Center, St Louis
🇺🇸St Louis, Missouri, United States
William Beaumont Hospital
🇺🇸Trey, Michigan, United States
VA Medical Center, Kansas City MO
🇺🇸Kansas City, Missouri, United States
New York Hospital Medical Center Of Queens
🇺🇸Flushing, New York, United States
VA Western New York Healthcare System at Buffalo
🇺🇸Buffalo, New York, United States
Torbay District General
🇬🇧Torbay, Devon, United Kingdom
Credit Valley Hospital Research Associates
🇨🇦Mississauga, Ontario, Canada
New York Harbor HCS
🇺🇸New York, New York, United States
VA Medical Center, Martinsburg
🇺🇸Martinsburg, West Virginia, United States
Blackpool Victoria Hospital
🇬🇧Blackpool, Lancashire, United Kingdom
VA Medical Center, Dayton
🇺🇸Dayton, Ohio, United States
University of Texas Medical Branch
🇺🇸Galveston, Texas, United States
VA Medical Center, Cleveland
🇺🇸Cleveland, Ohio, United States
VA Medical Center, Northport
🇺🇸Northport, New York, United States
VA Pittsburgh Health Care System
🇺🇸Pittsburgh, Pennsylvania, United States
VA South Texas Health Care System, San Antonio
🇺🇸San Antonio, Texas, United States
VA Medical Center, Portland
🇺🇸Portland, Oregon, United States
Wlliam S. Middleton Memorial Veterans Hospital, Madison
🇺🇸Madison, Wisconsin, United States
Surrey Memorial Hospital - Cardiology
🇨🇦Surrey, British Columbia, Canada
Bramptom, Research Associates
🇨🇦Brampton, Ontario, Canada
Queen Elizabeth II HSC
🇨🇦Halifax, Nova Scotia, Canada
Cardiology Consultants
🇨🇦Calgary, Alberta, Canada
Niagara Falls Medical Center
🇨🇦Niagara Falls, Ontario, Canada
Ottawa Heart Institute
🇨🇦Ottawa, Ontario, Canada
Invascor Clinical Research Inc.
🇨🇦Longeuil, Quebec, Canada
Etobicoke General Hospital
🇨🇦Rexdale, Ontario, Canada
Grey Nuns Com. Hospital and Health Centre
🇨🇦Edmonton, Alberta, Canada
Ajax and Pickering General Hospital
🇨🇦Ajax, Ontario, Canada
London HSC - University Campus
🇨🇦London, Ontario, Canada
Luton and Dunstable Hospital
🇬🇧Luton, Beds, United Kingdom
Derbyshire Royal Infirmary
🇬🇧Derby, United Kingdom
Hamilton Health Sciences Corp. - General Div
🇨🇦Hamilton, Ontario, Canada
Neureka Research Inc. Willett Green Millr Cntr
🇨🇦Sudbury, Ontario, Canada
Royal Victoria Hospital
🇬🇧Belfast, Antrim, United Kingdom
Royal University Hospital
🇨🇦Saskatoon, Saskatchewan, Canada
South Cleveland Hospital
🇬🇧Middlesborough, Cleveland, United Kingdom
Northwick Park Hospital and Institue for Medical R
🇬🇧Harrow, Middlesex, United Kingdom
St. James' University Hospital
🇬🇧Leeds, West Yorkshire, United Kingdom
Barnsley District General
🇬🇧Barnsley, South Yorkshire, United Kingdom
Cardiology Research Unit Sussex House
🇬🇧Brighton, Sussex, United Kingdom
Derriford Hospital
🇬🇧Devon, United Kingdom
Glasgow Western Infirmary
🇬🇧Glasgow, United Kingdom
Pinderfields General Hospital
🇬🇧Wakefield, United Kingdom
Pontefract General Infirmary
🇬🇧Pontefract, West Yorshire, United Kingdom
Northern General Hospital
🇬🇧Sheffield, Yorkshire, United Kingdom
St. Thomas' Hospital
🇬🇧London, United Kingdom
VA Medical Center, Oklahoma City
🇺🇸Oklahoma City, Oklahoma, United States
Southern Arizona VA Health Care System, Tucson
🇺🇸Tucson, Arizona, United States
Rancho Los Amigos National Rehabilitation Center
🇺🇸Downey, California, United States
VA Palo Alto Health Care System
🇺🇸Palo Alto, California, United States
VA Greater Los Angeles HCS, Sepulveda
🇺🇸Sepulveda, California, United States
Cardiology Associates of Derby, P.C.
🇺🇸Derby, Connecticut, United States
North Florida/South Georgia Veterans Health System
🇺🇸Gainesville, Florida, United States
VA Connecticut Health Care System (West Haven)
🇺🇸West Haven, Connecticut, United States
VA Medical Center, Bay Pines
🇺🇸Bay Pines, Florida, United States
VA Medical Center, DC
🇺🇸Washington, District of Columbia, United States
Florida Cardiovascular Research
🇺🇸Atlantis, Florida, United States
Watson Clinic LLP
🇺🇸Lakeland, Florida, United States
St. Francis Hospital and Medical Center
🇺🇸Hartford, Connecticut, United States
Brevard Cardiology
🇺🇸Merritt Island, Florida, United States
Cardiology Consultants - Pensacola
🇺🇸Pensacola, Florida, United States
University Cardiology Consultants
🇺🇸Tamarac, Florida, United States
VA Medical Center, Augusta
🇺🇸Augusta, Georgia, United States
Atlanta VA Medical and Rehab Center, Decatur
🇺🇸Decatur, Georgia, United States
Edward Hines, Jr. VA Hospital
🇺🇸Hines, Illinois, United States
Edith Nourse Rogers Memorial Veterans Hospital, Bedford
🇺🇸Bedford, Massachusetts, United States
Overton Brooks VA Medical Center, Shreveport
🇺🇸Shreveport, Louisiana, United States
River Cities Cardiology
🇺🇸Jeffersonville, Indiana, United States
Jesse Brown VAMC (WestSide Division)
🇺🇸Chicago, Illinois, United States
Heart Care Midwest
🇺🇸Peoria, Illinois, United States
VA Ann Arbor Healthcare System
🇺🇸Ann Arbor, Michigan, United States
VA Boston Healthcare System, Brockton Campus
🇺🇸Brockton, Massachusetts, United States
Bay State Medical Center
🇺🇸Springfield, Massachusetts, United States
Univ of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
VA Medical Center, Muskogee
🇺🇸Muskogee, Oklahoma, United States
VA Medical Center, Providence
🇺🇸Providence, Rhode Island, United States
Hunter Holmes McGuire VA Medical Center
🇺🇸Richmond, Virginia, United States
DUCCS Research of South Boston
🇺🇸South Boston, Virginia, United States
North Shore Cardiology Laboratory
🇨🇦North Vancouver, British Columbia, Canada
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
St. Joseph's Hospital
🇨🇦Hamilton, Ontario, Canada
Hotel-Dieu D'Artabaska
🇨🇦Victoriaville, Quebec, Canada
Regina General Hospital
🇨🇦Regina, Saskatchewan, Canada
Newham General Hospital
🇬🇧Plaistow, London, United Kingdom
Stepping Hills Hospital
🇬🇧Stockport, Cheshire, United Kingdom
York District Hospital
🇬🇧York, North Yorkshire, United Kingdom
Royal Alexandra Hospital
🇬🇧Paisley, Renfrewshire, United Kingdom
Princess of Wales Hospital (Grimsby)
🇬🇧Grimsby, South Humberside, United Kingdom
Bridlington and District Hospital
🇬🇧Bridlington, United Kingdom
Cardiology Research Associates
🇨🇦Scarborough, Ontario, Canada
Castle Hill Hospital
🇬🇧Cottingham, Hull, United Kingdom