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You Can’t Get Away with Dual Antiplatelet Therapy for Atrial Fibrillation
Data from the ACTIVE W trial show us why.
Oral anticoagulation therapy reduces the risk for stroke in patients with atrial fibrillation, but warfarin use can be inconvenient and increases bleeding risk. Given these concerns, researchers enrolled patients with atrial fibrillation and at least one stroke risk factor in an open-label randomized trial comparing dual antiplatelet therapy (75 mg of clopidogrel plus 75–100 mg of aspirin daily) with oral anticoagulation therapy, which is usually warfarin (target INR, 2–3).
The trial, known by the acronym ACTIVE W and funded by the makers of clopidogrel, was stopped after enrolling 6706 patients (median follow-up, 1.3 years) because anticoagulation was clearly superior to dual antiplatelet therapy. The anticoagulation group had significantly lower annual incidences of stroke than did the antiplatelet-therapy group (1.4% vs. 2.4%) and of the primary endpoint, a combination of stroke, non-CNS embolism, myocardial infarction, or death from vascular causes (3.9% vs. 5.6%). Major bleeding incidence was similar with anticoagulation (2.2%) and dual antiplatelet therapy (2.4%).
Comment: This important trial dashes hopes that more-powerful antiplatelet therapy can safely replace anticoagulation for preventing stroke in patients with atrial fibrillation. Cumulative evidence from atrial fibrillation trials shows that anticoagulation is required for prevention of thromboembolism secondary to blood stasis in the left atrium. The current trial’s results complement findings from other recent trials (Lancet 2004; 364:331 and N Engl J Med 2006; 354:1706). Collectively, these results show that for secondary stroke prevention, the commonly used but unproven combination of clopidogrel and aspirin is associated with a surprisingly high rate of major hemorrhage and should be avoided.
— Marc I. Chimowitz, MBChB
Dr. Chimowitz is Professor of Neurology at Emory University School of Medicine, Atlanta, GA.
Published in Journal Watch Neurology September 6, 2006
Citation(s):
ACTIVE Writing Group on behalf of the ACTIVE Investigators. 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 Jun 10; 367:1903-12.
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