A meta-analysis of nearly 80,000 patients published in the Nov. 17 issue of the Journal of the American College of Cardiology adds to a growing body of research seeking to evaluate and understand possible sex differences associated with antiplatelet therapies. This analysis found it to be effective in reducing cardiovascular events in both men and women with no statistically significant sex differences in terms of expected clinical benefit or increased harm.
Clopidogrel (Plavix; Bristol-Myers Squibb and Sanofi-Aventis) reduced cardiovascular events by 16 percent in men compared to 7 percent in women; however, this difference was not statistically significant, according to Jeffrey S. Berger, MD, from New York University School of Medicine in New York City, and colleagues.
This study was a meta-analysis of all blinded randomized clinical trials comparing clopidogrel and placebo (CURE, CREDO, CLARITY-TIMI 28, COMMIT and CHARISMA trials), involving a total of 79,613 patients, of whom 30 percent were women.
Although there was a “clear reduction” in the risk of cardiovascular events in both sexes, according to the authors, women derived the most benefit from a decrease in their risk of heart attack with a non-significant reduction in stroke and total death.
They found that the data showed a small but “real excess risk” of major bleeding with clopidogrel therapy in both men and women; adding clopidogrel to aspirin therapy resulted in a 43 percent and 21 percent increased risk of major bleeding in women and men, respectively.
According to the authors, by treating 1,000 men and 1,000 women with clopidogrel on a background of aspirin for an average of eight months, clinicians can prevent eight cardiovascular events in women and 12 in men; from a safety perspective, there would be five major bleeding incidents in women and two in men.
Researchers performed a meta-analysis of five major clinical trials to evaluate the clinical benefit and risk of this antiplatelet therapy in women and men and determine whether there are sex-based differences in treatment response. Nearly 80,000 individuals with a broad range of cardiovascular diseases were enrolled in these trials, 30 percent of whom were women. Lead investigators of the five double-blinded, randomized placebo-controlled trials shared original study data with authors.
Clopidogrel works to disrupt platelet activity and prevents them from clotting and causing heart attacks and strokes. It is typically used in patients with heart attacks, those at increased severity of angina, and in patients following stent implantation. It is also commonly used in those with established cardiovascular disease.
In the accompanying editorial, David P. Faxon, MD, from the division of cardiology at Brigham and Women's Hospital in Boston, wrote that while the cumulative evidence continues to show that women with coronary artery disease differ from men in many important ways—including the response to antiplatelet therapy—clopidogrel is an exception.
Faxon also noted that it is “critically important" that future studies are designed to adequately address the responses to therapy in women because “outcomes cannot be predicted by mostly male-dominated trials. Only then can treatment be optimized for the growing population of women with cardiovascular disease.”