Published Online
on March 16, 2009

A more recent version of this article appeared on March 31, 2009

This Article Full Text (PDF) CME: Take the course for this article: Circulation: March 31, 2009, Volume 119, Number 12 All Versions of this Article: 119/12/1616    most recent CIRCULATIONAHA.108.801753v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Massie, B. M. Search for Related Content PubMed PubMed Citation Articles by Massie, B. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ACETYLSALICYLIC ACID WARFARIN Medline Plus Health Information Heart Failure Related Collections Other heart failure Cardiovascular Pharmacology Coumarins Related Article

Submitted on June 24, 2008
Accepted on January 12, 2009

Randomized Trial of Warfarin, Aspirin, and Clopidogrel in Patients With Chronic Heart Failure. The Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) Trial

Barry M. Massie MD, Joseph F. Collins ScD^*, Susan E. Ammon MS, RN, FNP, Paul W. Armstrong MD, John G.F. Cleland MD, Michael Ezekowitz MD, Syed M. Jafri MD, William F. Krol PhD, Christopher M. O'Connor MD, Kevin A. Schulman MD, Koon Teo MD, Stuart R. Warren Pharm D, for the WATCH Trial Investigators

From the Department of Veterans Affairs, San Francisco, Calif (B.M.M., S.E.A.); Cooperative Studies Program Coordinating Center, Veterans Affairs Medical Center, Perry Point, Md (J.F.C., W.F.K.); University of Alberta, Edmonton, Alberta, Canada (P.W.A.); Castle Hill Hospital, East Yorkshire, UK (J.G.F.C.); Lankenau Institute for Medical Research, Wynnewood, Pa (M.E.); Henry Ford Hospital, Detroit, Mich (S.M.J.); Duke University Medical Center, Durham, NC (C.M.O., K.A.S.); McMaster University Medical Center, Hamilton, Ontario, Canada (K.T.); and Cooperative Studies Program Clinical Research Pharmacy, Veterans Affairs Medical Center, Albuquerque, NM (S.R.W.).

^* To whom correspondence should be addressed. E-mail: joseph.collins2{at}va.gov.

Background—Chronic heart failure remains a major cause of mortality and morbidity. The role of antithrombotic therapy in patients with chronic heart failure has long been debated. The objective of this study was to determine the optimal antithrombotic agent for heart failure patients with reduced ejection fractions who are in sinus rhythm.

Methods and Results—This prospective, randomized clinical trial of open-label warfarin (target international normalized ratio of 2.5 to 3.0) and double-blind treatment with either aspirin (162 mg once daily) or clopidogrel (75 mg once daily) had a 30-month enrollment period and a minimum of 12 months of treatment. We enrolled 1587 men and women 18 years of age with symptomatic heart failure for at least 3 months who were in sinus rhythm and had left ventricular ejection fraction of 35%. The primary outcome was the time to first occurrence of death, nonfatal myocardial infarction, or nonfatal stroke. For the primary composite end point, the hazard ratios were as follows: for warfarin versus aspirin, 0.98 (95% CI, 0.86 to 1.12; P=0.77); for clopidogrel versus aspirin, 1.08 (95% CI, 0.83 to 1.40; P=0.57); and for warfarin versus clopidogrel, 0.89 (95% CI, 0.68 to 1.16; P=0.39). Warfarin was associated with fewer nonfatal strokes than aspirin or clopidogrel. Hospitalization for worsening heart failure occurred in 116 (22.2%), 97 (18.5%), and 89 (16.5%) patients treated with aspirin, clopidogrel, and warfarin, respectively (P=0.02 for warfarin versus aspirin).

Conclusion—The primary outcome measure and the mortality data do not support the primary hypotheses that warfarin is superior to aspirin and that clopidogrel is superior to aspirin.

Key words: anticoagulants • aspirin • clopidogrel • heart failure • warfarin

Related Article:

Clinical Summaries
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