In patients with atrial fibrillation (AF) for whom vitamin K-antagonist therapy was unsuitable, the addition of clopidogrel (Plavix) to aspirin reduced the risk of major vascular events, especially stroke, and increased the risk of major hemorrhage, according to the ACTIVE trial published today in the New England Journal of Medicine.
Vitamin K antagonists reduce the risk of stroke in patients with AF but are considered unsuitable in many patients, who usually receive aspirin instead, according to the authors. The ACTIVE researchers investigated the hypothesis that the addition of clopidogrel to aspirin would reduce the risk of vascular events in patients with AF.
A total of 7,554 AF patients who had an increased risk of stroke and for whom vitamin K-antagonist therapy was unsuitable were randomly assigned to receive clopidogrel (75 mg) or placebo, once daily, in addition to aspirin, according to the authors. The primary outcome was the composite of stroke, MI, non-central nervous system systemic embolism or death from vascular causes.
At a median of 3.6 years of follow-up, the researchers reported that major vascular events had occurred in 6.8 percent of patients per year receiving clopidogrel and in 7.6 percent of patients per year receiving placebo (relative risk with clopidogrel, 0.89). The difference was primarily due to a reduction in the rate of stroke with clopidogrel.
The ACTIVE investigators found that stroke occurred in 2.4 percent of patients receiving clopidogrel and 3.3 percent of patients per year receiving placebo (relative risk, 0.72). MI occurred in 0.7 percent of patients per year receiving clopidogrel and in 0.9 percent of patients per year receiving placebo (relative risk, 0.78) -- the difference being nonsignificant. Major bleeding occurred in 2 percent of patients per year receiving clopidogrel and in 1.3 percent of patients per year receiving placebo (relative risk, 1.57).
The authors wrote that the addition of clopidogrel to aspirin in AF patients "results in a significantly greater reduction in platelet aggregation than that observed with aspirin alone, suggesting that more effective platelet inhibition could augment the protective effect of aspirin. The results of ACTIVE confirm this hypothesis and provide strong evidence for an important role of abnormal platelet activation in the pathogenesis of stroke in AF patients."
Bristol-Myers Squibb and Sanofi-Aventis, the makers of Plavix, supported the study.