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

• Published in: Circulation (New York, N.Y.) Vol. 119; no. 12; pp. 1616 - 1624
• Main Authors: MASSIE, Barry M, COLLINS, Joseph F, TEO, Koon, WARREN, Stuart R, AMMON, Susan E, ARMSTRONG, Paul W, CLELAND, John G. F, EZEKOWITZ, Michael, JAFRI, Syed M, KROL, William F, O'CONNOR, Christopher M, SCHULMAN, Kevin A
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 31.03.2009
• Subjects: Adult; Aged; Aged, 80 and over; Aspirin - administration & dosage; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular system; Chronic Disease; Death; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Double-Blind Method; Female; Fibrinolytic Agents - administration & dosage; Heart Failure - complications; Heart Failure - drug therapy; Heart Failure - mortality; Humans; Male; Medical sciences; Middle Aged; Myocardial Infarction; Pharmacology. Drug treatments; Stroke; Stroke Volume; Ticlopidine - administration & dosage; Ticlopidine - analogs & derivatives; Vasodilator agents. Cerebral vasodilators; Warfarin - administration & dosage; Prostaglandin-endoperoxide synthase; Coumarine derivatives; Cardiovascular disease; Anticoagulant; Acetylsalicylic acid; Antivitamin K; Heart disease; Antithrombotic agent; anticoagulants; aspirin; Salicylates; Human; Heart failure; Warfarin; Enzyme; Enzyme inhibitor; Antiplatelet agent; Non steroidal antiinflammatory agent; Chronic; Analgesic; Treatment; Antipyretic; Clopidogrel; Oxidoreductases; Thienopyridine derivative
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.108.801753

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. 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). 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.