Plavix-Aspirin Called Poor Substitute for Anticoagulants to Prevent Stroke in A-Fib

HAMILTON, Ontario, June 9 ? Plavix (clopidogrel) plus aspirin antiplatelet therapy is a poor alternative to oral anticoagulation for preventing stroke and other vascular events in atrial fibrillation patients, according to researchers here.

Compared with patients taking Coumadin (warfarin), those taking Plavix plus aspirin were 44% more likely to suffer a vascular event such as a stroke, heart attack, or embolism over the course of about a year, said Stuart J. Connolly, M.D., of the Hamilton Health Sciences Corporation here, and colleagues.

The researchers were looking for an alternative to oral anticoagulant therapy to prevent stroke in patients with atrial fibrillation because of the significantly increased risk for major bleeding associated with this treatment, Dr. Connolly and colleagues said in the June 10 issue of The Lancet.

The study involved more than 6,700 patients with atrial fibrillation in more than 30 countries participating in the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE W) study. All patients were 75 or older, and all had at least one other risk factor for stroke such as hypertension or a previous stroke.

Half the participants were randomized to the anticoagulant used in their country?most commonly Coumadin and Avapro (irbesartan). The other half received Plavix plus aspirin. Patients were followed for an average of a little more than a year during 2003 and 2004, although some were followed for two years.

There were 243 adverse vascular events in the antiplatelet group?including stroke, embolism, MI, and vascular death?compared with 164 in the anticoagulant group (relative risk=1.44; 95% confidence interval=1.18 to 1.76; P=.0003), the investigators reported.

The increased risk in the antiplatelet group was most notable for stroke (RR=1.72; 95% CI=1.24 to 2.37; P=.001) and for non-central nervous system systemic embolism (RR=4.66; 95% CI=1.58 to 13.8; P=.005), the study found.

The anticoagulant group was not at significantly greater risk for major hemorrhage compared with the antiplatelet group (RR=0.34; 95% CI=0.12 to 0.93; P=.036), the study found.

"Our findings clearly showed that oral anticoagulation therapy was a better treatment than clopidogrel plus aspirin for the population we investigated," the authors concluded.

"Both the lack of efficacy of the aspirin and clopidogrel combination and the bleeding risk of the dual antiplatelet treatment in ACTIVE W are a disappointment," said Freek W.A. Verheugt, M.D., of the University Medical Center St. Radboud in Nijmegen, The Netherlands, in an editorial.

"Thus warfarin remains the standard of antithrombotic care for all eligible patients with atrial fibrillation," Dr. Verheugt said. "New developments are to be expected from innovative oral direct-thrombin blockers or oral factor-Xa inhibitors, rather than from available antiplatelet agents."

The study was supported by Bristol-Myers Squibb and Sanofi-Aventis. Bristol-Myers Squibb markets Coumadin, and both companies jointly market Avapro and Plavix.