Warfarin versus aspirin in patients with reduced cardiac ejection fraction (WARCEF): rationale, objectives, and design.
BACKGROUND
Warfarin is widely prescribed for patients with heart failure without level 1 evidence, and an adequately powered randomized study is needed.


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 < or =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.


CONCLUSIONS
The results should help guide the selection of optimum antithrombotic therapy for patients with left ventricular dysfunction.
Pullicino
Patrick
P
Department of Neurology and Neurosciences, New Jersey Medical School, UMDNJ, Newark, USA.
Thompson
John L P
JL
Barton
Bruce
B
Levin
Bruce
B
Graham
Susan
S
Freudenberger
Ronald S
RS
D000925:Anticoagulants / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D002303:Cardiac Output, Low / Q000188:drug therapy* / Q000503:physiopathology*; D004311:Double-Blind Method; D005260:Female; D006040:Goals; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D012107:Research Design; D013318:Stroke Volume; D014859:Warfarin / Q000627:therapeutic use*
D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D014859:Warfarin; D001241:Aspirin