No Gender Gap Found for Clot-Busting Drug
MONDAY Nov. 9, 2009 -- The widely used clot-dissolving drug Plavix (clopidogrel) works about the same in women as in men, an analysis of major clinical trials has found.
"After this study, I can say we can be confident in treating both men and women with this very important drug," said Dr. Jeffrey S. Berger, director of cardiovascular thrombosis at New York University Langone Medical Center in New York City and lead author of a report in the Nov. 17 issue of the Journal of the American College of Cardiology.
Clopidogrel acts by preventing blood cells called platelets from forming clots that block arteries. It is one of several antiplatelet drugs; aspirin is another. Clopidogrel is commonly prescribed to prevent clots in people with the abnormal heartbeat called unstable angina, or after a heart attack or the implant of a stent, a thin tube put in to keep arteries open.
The study looked at data from five major clinical trials of clopidogrel involving nearly 60,000 people, 30 percent of them women. Leaders of the trials worked together to determine how the drug worked in men and women.
"There have been a lot of preliminary suggestive data that men and women respond differently to antiplatelet medications," Berger said. "Up to this point, there have been no data on the benefits and risks of clopidogrel in women and in men. Is there a difference? Overall, we can say the answer is no."
The study is the latest example of the growing attention being paid to cardiovascular problems such as heart attack and stroke in women, a subject often overlooked in the past. Attention is being paid, Berger said, because a third to half of all heart attacks occur in women. Two recent studies reported that the incidence of heart attacks has increased in American women in the past two decades, while their chance of surviving heart attacks has improved.
At first glance, the raw data from the studies would seem to indicate a difference in male vs. female response to Plavix. The drug reduced cardiovascular events by 16 percent in men and 7 percent in women. The chief benefit for women was reduction of heart attack risk; for men it was reduction of strokes and cardiovascular deaths.
"But you have to look at the absolute benefit," Berger said. "What is the absolute difference? If we treat 1,000 men for eight months, we prevent 12 cardiovascular events. If we treat 1,000 women, we prevent eight cardiovascular events. We are not saying there are no differences between men and women. We are saying there are no significant differences."
The significance of the differences was of major concern to the cardiologists who did the study, Berger said. "We really discussed this at length, how to convey this data," he said.
The major risk of Plavix and other antiplatelet drugs is excess bleeding. The raw data showed that adding Plavix to aspirin increased the risk of major bleeding in women by 43 percent and in men by 21 percent.
"If you treat 1,000 men, you will have approximately five major bleeding events, and if you treat 1,000 women, you will have two major bleeding events," Berger said.
In an accompanying editorial, Dr. David P. Faxon, vice chairman of medicine at Brigham and Women's Hospital in Boston, wrote that "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."
"The good news is that clopidogrel is an exception," he wrote.
Adequate numbers of women need to be included in future cardiovascular studies "because outcomes cannot be predicted by mostly male-dominated trials," the editorial continued.
The new study doesn't settle the issue entirely, Faxon said. "A meta-analysis, putting together data from many different trials, is never as good as a randomized trial," he explained. Such a trial would be desirable, he said, because there are gender-related differences in blood vessels and cells.
"Women have more reactive platelets, and more delicate blood vessels," Faxon said.
But both Faxon and Berger said they do not consider the gender of a patient when they prescribe clopidogrel.
However, including women in studies of antiplatelet drugs is important, Berger said, because clopidogrel is expected to be available in a less-expensive, generic version, which will widen its use, and because more powerful antiplatelet medications are just becoming available.
The U.S. National Library of Medicine has more on the benefits and risks of clopidogrel.
Posted: November 2009