PLAVIX IN MEN VS. WOMEN

November 10, 2009 (New York, New York) — A new meta-analysis of the major clopidogrel trials has suggested that the drug reduces cardiovascular events and increases bleeding in both men and women, without significant differences between the sexes [1].

The study, published in the November 17, 2009 issue of the Journal of the American College of Cardiology, was conducted by a group led by Dr Jeffrey Berger (New York University School of Medicine, NY).

Berger commented to heartwire : "Preliminary data suggest that men and women respond differently to antiplatelet drugs. This has been seen with aspirin and with GP IIb/IIIa blockers. So we wanted to look at clopidogrel in this regard, because it is a commonly used medication and whether it has differential effects on men and women has not been studied to date." He added: "We saw small differences, but they were nonsignificant and could have easily occurred by the play of chance. Overall, we can say that, from 80 000 patients studied, clopidogrel is effective in reducing cardiovascular events and confers an increased risk of bleeding in both men and women."

The meta-analysis included the major placebo-controlled clopidogrel trials--CURE, CREDO, CLARITY TIMI 28, COMMIT, and CHARISMA--in a total of 79 613 patients, of whom 30% were women.

Results showed that in the overall population, clopidogrel was associated with a highly significant 14% proportional reduction in the risk of cardiovascular events (cardiovascular death, MI, or stroke), with no significant differences in treatment effect between women and men. Among the 23 533 women enrolled, the risk reduction with clopidogrel seemed to be greatest for MI, with the effects on stroke or death not statistically significant. Among the 56 091 men enrolled, the risk reduction was significant for MI, stroke, and death individually. Clopidogrel increased the risk of major bleeding in both women and men.

Effects of Clopidogrel on CV Events and Bleeding Risk in Men vs Women

Outcome	Odds ratio	95% CI
Overall population (n=79 613) CV death/MI/stroke	0.86	0.80–0.93
Women (n=23 533)
CV death/MI/stroke	0.93	0.86–1.01
MI	0.81	0.70–0.93
Stroke	0.91	0.69–1.21
Death	0.99	0.90–1.08
Men (n=56 091)
CV death/MI/stroke	0.84	0.78–0.91
MI	0.83	0.76–0.92
Stroke	0.83	0.71–0.96
Death	0.91	0.84–0.97
Bleeding risk
Women	1.43	1.15–1.79
Men	1.22	1.05–1.42

Berger commented to heartwire : "We did show some differences in the point estimates. For example, clopidogrel was associated with a 16% reduced occurrence of cardiovascular events in men, vs a 7% reduction in women. And bleeding was increased with clopidogrel by 22% in men and 43% in women. But because these differences were not significant, we cannot say the drug is more effective in men than in women."

He added: "Obviously, every healthcare provider needs to look at every individual patient and try to see how each patient fits in, and women tend to be at higher risk of bleeding complications in general. But I would certainly not hesitate to treat women with clopidogrel. We have been treating women with this drug, and our data are reassuring in that they suggest we need to continue that practice."

But Berger noted that because of their increased bleeding risk, he would be more cautious about the newer, more potent antiplatelet drugs, such as prasugrel and ticagrelor, in women. "The data on these drugs in women will be interesting. For example, we know in TRITON that the bleeding risk was higher with prasugrel in smaller and older patients, and the women we treat tend to be smaller and older than the men," he said.

Asked how these latest data on clopidogrel fit in with the differential effects seen with aspirin and GP IIb/IIIa blockers in the two sexes, Berger explained that the data on aspirin suggest that it is of benefit in both sexes but in men it tends to reduce cardiovascular events, while in women it tends to reduce stroke. Differences between the sexes have also been seen with GP IIb/IIIa blockers in ACS, with men benefiting more than women, but Berger said this was probably accounted for by the fact that men were higher risk in terms of testing positive for troponin, and this is the group that benefits from GP IIb/IIIa blockers.

"I don't think it is a matter of saying that a particular drug works in men but not women. I think it is rather that the pathology of heart disease is different in men and women, and we need to treat different pathologies in separate ways," he added.

Berger has received research support from AstraZeneca, is a consultant to Accumetrics, the Medicines Company, Eli Lilly/Daiichi Sankyo, and Novartis/Portola, and has received research funding from Thrombovision, Helena, Accumetrics, AstraZeneca, Haemoscope, the Medicines Company, Corgenix/Aspirin Works, and Eli Lilly/Daiichi Sankyo. Disclosures for the coauthors are listed in the paper.