Warfarin prevents more strokes than clopidorel+ASA in a fib (ACTIVE)

Clinical Question

Is warfarin better than clopidogrel plus aspirin in preventing strokes in patients with atrial fibrillation?

Bottom Line

Warfarin is superior to the combination of clopidogrel (Plavix) plus aspirin in preventing strokes and systemic emboli in high-risk patients with atrial fibrillation. (LOE = 2b)


ACTIVE Writing Group on behalf of the ACTIVE Investigators; Connolly S, Pogue J, Hart R, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006;367:1903-1912.  [PMID:16765759]

Study Design

Randomized controlled trial (nonblinded)






Outpatient (any)


In this study, more than 6700 patients with atrial fibrillation eligible for -- and willing to take -- oral anticoagulation were included if they had at least one of the following characteristics: more than 75 years of age; treated for hypertension; a previous stroke, transient ischemic attack, or non-CNS systemic embolism; left ventricular ejection fraction less than 45%; or peripheral artery disease. They also included younger patients if they had diabetes or coronary artery disease. Eligible patients were randomly assigned to once-daily clopidogrel (75 mg) plus aspirin (75 to 100 mg daily) or warfarin titrated to a target international normalized ratio of between 2.0 and 3.0. The primary study outcomes (stroke, non-CNS systemic embolism, myocardial infarction, or vascular death), assessed by researchers masked to treatment assignment, were evaluated by intention to treat. The study was terminated early because of the clear superiority of oral anticoagulation. After 1.3 years of follow-up, bad outcomes occurred in 4.9% of patients taking oral anticoagulation compared with 7.0% in those treated with clopidogrel plus aspirin (number needed to treat = 48; 95% CI, 31-101). They found minimal differences in all individual events, except stroke and non-CNS embolism. The rate of major bleeding complications was comparable in patients taking clopidogrel plus aspirin (2.42% per year) and patients taking warfarin (2.21% per year). However, the rate of minor bleeding was lower in patients treated with warfarin (11.4% vs 13.6%).