title: Benefit of warfarin compared with aspirin in patients with heart failure in sinus rhythm: a subgroup analysis of WARCEF, a randomized controlled trial.
abstract: BACKGROUND
  The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial found no difference in the primary outcome between warfarin and aspirin in 2305 patients with reduced left ventricular ejection fraction in sinus rhythm. However, it is unknown whether any subgroups benefit from warfarin or aspirin.
  
  
  RESULTS
  We used a Cox model stepwise selection procedure to identify subgroups that may benefit from warfarin or aspirin on the WARCEF primary outcome. A secondary analysis added major hemorrhage to the outcome. The primary efficacy outcome was time to the first to occur of ischemic stroke, intracerebral hemorrhage, or death. Only age group was a significant treatment effect modifier (P for interaction, 0.003). Younger patients benefited from warfarin over aspirin on the primary outcome (4.81 versus 6.76 events per 100 patient-years: hazard ratio, 0.63; 95% confidence interval, 0.48-0.84; P=0.001). In older patients, therapies did not differ (9.91 versus 9.01 events per 100 patient-years: hazard ratio, 1.09; 95% confidence interval, 0.88-1.35; P=0.44). With major hemorrhage added, in younger patients the event rate remained lower for warfarin than aspirin (5.41 versus 7.25 per 100 patient-years: hazard ratio, 0.68; 95% confidence interval, 0.52-0.89; P=0.005), but in older patients it became significantly higher for warfarin (11.80 versus 9.35 per 100 patient-years: hazard ratio, 1.25; 95% confidence interval, 1.02-1.53; P=0.03).
  
  
  CONCLUSIONS
  In patients <60 years, warfarin improved outcomes over aspirin with or without inclusion of major hemorrhage. In patients ≥60 years, there was no treatment difference, but the aspirin group had significantly better outcomes when major hemorrhage was included.
authors.affiliation: the Division of Cardiology, Department of Medicine.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Homma
authors.forename: John L P
authors.initials: JL
authors.lastname: Thompson
authors.forename: Alexandra R
authors.initials: AR
authors.lastname: Sanford
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Mann
authors.forename: Ralph L
authors.initials: RL
authors.lastname: Sacco
authors.forename: Bruce
authors.initials: B
authors.lastname: Levin
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Pullicino
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Freudenberger
authors.forename: John R
authors.initials: JR
authors.lastname: Teerlink
authors.forename: Susan
authors.initials: S
authors.lastname: Graham
authors.forename: J P
authors.initials: JP
authors.lastname: Mohr
authors.forename: Barry M
authors.initials: BM
authors.lastname: Massie
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Labovitz
authors.forename: Marco R
authors.initials: MR
authors.lastname: Di Tullio
authors.forename: André P
authors.initials: AP
authors.lastname: Gabriel
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
authors.forename: Conrado J
authors.initials: CJ
authors.lastname: Estol
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Lok
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000209:etiology / Q000517:prevention & control; D002543:Cerebral Hemorrhage / Q000209:etiology / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000517:prevention & control; D013318:Stroke Volume; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D001241:Aspirin
keywords: aspirin; heart failure; sinus rhythm; stroke; warfarin