Description: Question What are the relative efficacy and safety of warfarin and aspirin in patients with heart failure who are in sinus rhythm? Methods Design Randomized controlled trial (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction [WARCEF] trial). ClinicalTrials.gov NCT00041938. Allocation {Concealed}*.† Blinding Blinded† (patients, clinicians, {data collectors, safety committee}*, and outcome assessors). Follow-up period ≤ 6 years (mean 3.5 y). Setting 168 centers in the USA, Canada, Argentina, and Europe. Patients 2305 adults ≥ 18 years of age (mean age 61 y, 80% men) who had a left ventricular ejection fraction (LVEF) ≤ 35% and normal sinus rhythm, and planned treatment with a β-blocker, angiotensin-converting enzyme inhibitor, or hydralazine and nitrates. Exclusion criteria included modified Rankin score 〉 4, medical conditions with high risk for cardiac embolism, clear indication for warfarin or aspirin, or contraindication to warfarin. Patients in New York Heart Association class I were eligible but could not comprise 〉 20% of randomized patients. Intervention Active warfarin (with target international normalized ratio 2.0 to 3.5) plus aspirin placebo ( n = 1142), or aspirin, 325 mg/d, plus warfarin placebo ( n = 1163). Outcomes Primary composite endpoint of ischemic stroke, intracerebral hemorrhage (ICH), or death. Secondary outcome was a composite of ischemic stroke, ICH, death, myocardial infarction, or hospitalization for heart failure. The safety outcome was a composite of ischemic stroke, ICH, death, or intracranial hemorrhage. The trial had 69% power to detect a relative hazard reduction of 17.8% in the primary outcome and 83% power for the secondary outcome. Patient follow-up {93%}* (96% for vital status; intention-to-treat analysis). Main results Enrolment was stopped early because of slow recruitment. Groups did not differ for the primary composite outcome or any of its components except for ischemic stroke (Table). Groups also did not differ for the secondary or safety composite endpoints (Table). Conclusion In patients with heart failure who are in sinus rhythm, warfarin and aspirin did not differ for a composite of death or ischemic or hemorrhage outcomes.Warfarin vs aspirin in patients with heart failure who are in sinus rhythm‡OutcomesEvents / 100 patient-yAt a mean 3.5 yWarfarinAspirinRRR (95% CI)NNT (CI)Primary composite§7.57.9{4% (−10 to 16)}||Not significantSafety composite¶7.68.0{3% (−11 to 15)}||Not significantRRI (CI)NNH (CI)Secondary composite**12.712.2{5% (−6 to 16)}||Not significant‡Abbreviations defined in Glossary.§Ischemic stroke {0.7 vs 1.4, RRR 46%, 95% CI 16 to 65}||, intracerebral hemorrhage {0.12 vs 0.05, RRI 155%, CI −51 to 1210}||, or death {6.6 vs 6.5, RRI 4%, CI −11 to 20}||.||Estimates provided by author.¶Ischemic stroke, intracerebral hemorrhage, death, or intracranial hemorrhage.**Ischemic stroke, intracerebral hemorrhage, death, myocardial infarction, or hospitalization for heart failure.