Warfarin Versus Aspirin in Patients With Reduced Cardiac Ejection Fraction (WARCEF): Rationale, Objectives, and Design

Abstract

Background Warfarin is widely prescribed for patients with heart failure without level 1 evidence, and an adequately powered randomized study is needed. Methods and Results The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction study is a National Institutes of Health–funded, randomized, double-blind clinical trial with a target enrollment of 2860 patients. It is designed to test with 90% power the 2-sided primary null hypothesis of no difference between warfarin (International Normalized Ratio 2.5–3) and aspirin (325 mg) in 3- to 5-year event-free survival for the composite endpoint of death, or stroke (ischemic or hemorrhagic) among patients with cardiac ejection fraction ≤35% who do not have atrial fibrillation or mechanical prosthetic heart valves. Secondary analyses will compare warfarin and aspirin for reduction of all-cause mortality, ischemic stroke, and myocardial infarction (MI), balanced against the risk of intracerebral hemorrhage, among women and African Americans; and compare warfarin and aspirin for prevention of stroke alone. Randomization is stratified by site, New York Heart Association (NYHA) heart class (I vs II-IV), and stroke or transient ischemic attack (TIA) within 1 year before randomization versus no stroke or TIA in that period. NYHA class I patients will not exceed 20%, and the study has a target of 20% (or more) patients with stroke or TIA within 12 months. Randomized patients receive active warfarin plus placebo or active aspirin plus placebo, double-blind. Conclusion The results should help guide the selection of optimum antithrombotic therapy for patients with left ventricular dysfunction.