Warfarin and Antiplatelet Therapy in Chronic Heart Failure

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00007683
Recruitment Status : Completed
First Posted : January 1, 2001
Last Update Posted : June 16, 2011
Bristol-Myers Squibb
Information provided by:
VA Office of Research and Development

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).

Condition or disease Intervention/treatment Phase
Heart Failure Drug: Warfarin titrated to an INR of 2.5-3.0 Drug: Aspirin Drug: Clopidogrel 75 Phase 3

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1587 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: CSP #442 - Warfarin and Antiplatelet Therapy Study in Patients With Congestive Heart Failure (WATCH)
Study Start Date : October 1998
Actual Primary Completion Date : July 2003
Actual Study Completion Date : December 2004

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: 1
Warfarin Titrated to an INR of 2.5-3.0
Drug: Warfarin titrated to an INR of 2.5-3.0
anticoagulation (administered without blinding) titrated to a target INR of 2.5 to 3.0, monitored by measurements at 6 week intervals after initial titration and stabilization.
Active Comparator: 2
Aspirin 182 mg
Drug: Aspirin
an antiplatelet agent whose mechanism is inhibition of thromboxane, a platelet activator) administered in a double blind manner.
Active Comparator: 3
Clopidogrel 75 mg
Drug: Clopidogrel 75
(an antiplatelet agent whose mechanism is ADP inhibition) administered in a double blind manner)

Primary Outcome Measures :
  1. acomposite of mortality, nonfatal myocardial infarction and nonfatal stroke [ Time Frame: 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.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

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.

Exclusion Criteria:

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00007683

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United States, Alabama
VA Medical Center, Birmingham
Birmingham, Alabama, United States, 35233
United States, Arizona
Carl T. Hayden VA Medical Center
Phoenix, Arizona, United States, 85012
Southern Arizona VA Health Care System, Tucson
Tucson, Arizona, United States, 85723
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Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock
No. Little Rock, Arkansas, United States, 72114-1706
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Rancho Los Amigos National Rehabilitation Center
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VA Palo Alto Health Care System
Palo Alto, California, United States, 94304-1290
VA Medical Center, San Francisco
San Francisco, California, United States, 94121
VA Greater Los Angeles HCS, Sepulveda
Sepulveda, California, United States, 91343
Cardiovascular Consultants, Walnut Creek
Walnut Creek, California, United States, 94598
VA Greater Los Angeles Healthcare System, West LA
West Los Angeles, California, United States, 90073
United States, Colorado
VA Eastern Colorado Health Care System, Denver
Denver, Colorado, United States, 80220
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Cardiology Associates of Derby, P.C.
Derby, Connecticut, United States, 06418
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Hartford, Connecticut, United States, 06120
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West Haven, Connecticut, United States, 06516
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Washington, District of Columbia, United States, 20422
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Florida Cardiovascular Research
Atlantis, Florida, United States, 33462
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Bay Pines, Florida, United States, 33708
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Watson Clinic LLP
Lakeland, Florida, United States, 33805
Brevard Cardiology
Merritt Island, Florida, United States, 32952
VA Medical Center, Miami
Miami, Florida, United States, 33125
Cardiology Consultants - Pensacola
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Tamarac, Florida, United States, 33321
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Tampa, Florida, United States, 33612
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Overton Brooks VA Medical Center, Shreveport
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Wlliam S. Middleton Memorial Veterans Hospital, Madison
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Calgary, Alberta, Canada, T2E 7C5
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Edmonton, Alberta, Canada, T6L 5X8
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Alder Medical Centre
Campbell River, British Columbia, Canada, V9W 6X8
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Scarborough, Ontario, Canada, M1S 4V5
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Sudbury, Ontario, Canada, P3E 6B4
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Toronto, Ontario, Canada, M5B 1W8
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Toronto, Ontario, Canada, M5T 2S8
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Longeuil, Quebec, Canada, J4N 1E1
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Montreal, Quebec, Canada, H1T 2M4
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Victoriaville, Quebec, Canada, G6P 6N2
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Regina General Hospital
Regina, Saskatchewan, Canada, S4P 0W5
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Saskatoon, Saskatchewan, Canada, S7K 0Z9
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Saskatoon, Saskatchewan, Canada, S7N 0W8
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Belfast, Antrim, United Kingdom, BT12 6BA
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Luton, Beds, United Kingdom, LU4 0DZ
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Selly Oak, Birmingham, United Kingdom, B29 6JD
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Stockport, Cheshire, United Kingdom, SK2 7JE
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Middlesborough, Cleveland, United Kingdom, TS4 3BW
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Torbay, Devon, United Kingdom, TQ2 7AA
King Geroge Hospital
Ilford, Essex, United Kingdom, IG3 8YB
Castle Hill Hospital
Cottingham, Hull, United Kingdom, HU16 5JG
Blackpool Victoria Hospital
Blackpool, Lancashire, United Kingdom, FY3 8NR
Newham General Hospital
Plaistow, London, United Kingdom, E13 8SL
Wythenshawe Hospital
Wythenshawe, Manchester, United Kingdom, M23 9LT
Northwick Park Hospital and Institue for Medical R
Harrow, Middlesex, United Kingdom, HA1 3UJ
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Scunthorpe, North Lincolnshire, United Kingdom, DN15 7BH
York District Hospital
York, North Yorkshire, United Kingdom, YO3 7HE
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Paisley, Renfrewshire, United Kingdom, PA2 9PN
Princess of Wales Hospital (Grimsby)
Grimsby, South Humberside, United Kingdom, DN33 2BA
Barnsley District General
Barnsley, South Yorkshire, United Kingdom, S75 2EP
Cardiology Research Unit Sussex House
Brighton, Sussex, United Kingdom, BN2 1ES
St. James' University Hospital
Leeds, West Yorkshire, United Kingdom, LS9 7TF
Pontefract General Infirmary
Pontefract, West Yorshire, United Kingdom, WF8 1PL
Northern General Hospital
Sheffield, Yorkshire, United Kingdom, S5 7AU
Bridlington and District Hospital
Bridlington, United Kingdom, YO16 4QP
Derbyshire Royal Infirmary
Derby, United Kingdom, DE1 2QY
Derriford Hospital
Devon, United Kingdom, PL6 8DH
Glasgow Western Infirmary
Glasgow, United Kingdom, G12 8QQ
St. Thomas' Hospital
London, United Kingdom, SE1 7EH
Pinderfields General Hospital
Wakefield, United Kingdom, WF1 4DG
Sponsors and Collaborators
VA Office of Research and Development
Bristol-Myers Squibb
Study Chair: Barry M. Massie, MD VA Medical Center, San Francisco

Publications of Results:
Other Publications:
Responsible Party: Massie, Barry - Study Chair, Department of Veterans Affairs Identifier: NCT00007683     History of Changes
Other Study ID Numbers: 442
First Posted: January 1, 2001    Key Record Dates
Last Update Posted: June 16, 2011
Last Verified: June 2011

Keywords provided by VA Office of Research and Development:
embolic events
Left ventricular ejection fraction less than or eq
symptomatic CHF

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents