title: Randomized trial of warfarin, aspirin, and clopidogrel in patients with chronic heart failure: the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial.
abstract: 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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Veterans Affairs, San Francisco, CA, USA.
authors.forename: Barry M
authors.initials: BM
authors.lastname: Massie
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Collins
authors.forename: Susan E
authors.initials: SE
authors.lastname: Ammon
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.forename: John G F
authors.initials: JG
authors.lastname: Cleland
authors.forename: Michael
authors.initials: M
authors.lastname: Ezekowitz
authors.forename: Syed M
authors.initials: SM
authors.lastname: Jafri
authors.forename: William F
authors.initials: WF
authors.lastname: Krol
authors.forename: Christopher M
authors.initials: CM
authors.lastname: O'Connor
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Schulman
authors.forename: Koon
authors.initials: K
authors.lastname: Teo
authors.forename: Stuart R
authors.initials: SR
authors.lastname: Warren
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage; D002908:Chronic Disease; D000077144:Clopidogrel; D003643:Death; D004311:Double-Blind Method; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction; D020521:Stroke; D013318:Stroke Volume; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014859:Warfarin / Q000008:administration & dosage
chemical_list: D005343:Fibrinolytic Agents; D014859:Warfarin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin