Aspirin Reduces Nonfatal MI in Studies of Men, but not in Trials Dominated by Women

October 23, 2007 — A new meta-analysis adds heft to concerns that aspirin does not benefit women in the same way it does men [1]; however, experts not involved in the study caution that the new research should not in any way change how physicians currently prescribe aspirin to women.
Writing in the October 18, 2007 issue of BMC Medicine, Dr Todd Yerman (University of Toronto, ON) and colleagues report that trials with a higher proportion of men were more likely to show a benefit of aspirin, while studies with more women showed no significantly reduced risk of myocardial infarction (MI).
"Gender accounts for a substantial proportion of the variability in the efficacy of aspirin in reducing MI rates across these trials and supports the notion that women might be less responsive to aspirin than men," the authors conclude.
But Dr Neica Goldberg (Total Heart Care, New York, NY), speaking on behalf of the American Heart Association (AHA), warned that physicians should not interpret these results to mean they should stop using aspirin in all women. "Physicians really have to make sure it's very clear to their patients why they are going on aspirin, so that information like this study, when it reaches the public media, doesn't cause the patient to discontinue her aspirin therapy when in fact she should continue it."
Aspirin's gender effects
In recent years, several trials and retrospective analyses have hinted that aspirin's role in women may be primarily for secondary prevention, not primary prevention, and predominantly in older women who already have cardiovascular risk factors; aspirin may also be more important as a means of preventing stroke, rather than MI, studies suggest.
In their study, Yerman et al reviewed any randomized, placebo-controlled trial of aspirin on MI risk published between 1966 and 2006, a search that yielded 23 trials. While aspirin appeared to reduce the risk of nonfatal MI in the cohort as a whole, it appeared to have no effect on fatal MI. To see whether gender balance within trials had an impact on aspirin efficacy, the authors divided the studies according to tertiles of gender mix, with trials with 0-66% male participants (eg, predominantly women) representing the lowest tertile and trials with 100% male participants representing the highest tertile. They found that in those trials with 100% men, aspirin had the greatest effect on nonfatal MI, whereas the tertile with the least men/most women failed to show any benefit of aspirin on nonfatal MI.
According to the authors, the reasons for aspirin's discordant results remain "largely a mystery," although some studies suggest that women have higher aspirin resistance, while others indicate that there are "structural and physiological" differences between male and female coronary vasculature, including the smaller size and greater stiffness of women's vessels.
"Our findings... suggest that clinicians should be cautious in prescribing aspirin in women, especially for primary prevention," Yerman and his coauthors conclude.
No new information to guide clinical practice
But commenting on the study for heartwire, Dr Julie E Buring (Brigham and Women's Hospital, Boston, MA), whose analysis of the Women's Health Study (WHS) was one of the pivotal studies to illuminate some of the apparently disparate effects of aspirin in men and women, noted that Berman et al's study offers some suggestions as to why the WHS analysis did not demonstrate a reduction in first MI in women. But those hypotheses, and in particular the possibility that women are more resistant to aspirin, "would take further basic research to demonstrate this one way or the other," she said.
Moreover, Buring added, a flaw in Berman et al's study is the fact that the authors did not differentiate between aspirin's effects in terms of primary and secondary prevention.
"I would separate any mechanistic message about a possible resistance to aspirin between the genders, from the clear public-health message that among survivors of a prior event, aspirin has been clearly shown for both genders to be beneficial in reducing risk of a subsequent event," Buring stressed. "And in primary prevention, the person should discuss with their healthcare provider whether they are a good candidate for aspirin therapy."
Goldberg, likewise, warned that aspirin studies like this one tend to make a major splash in the mainstream media, and physicians should make sure they are aware of the recent AHA guidelines on cardiovascular disease (CVD) management in women.
Those guidelines specify that aspirin should be given to both men and women who are experiencing an acute MI, and for men and women for secondary prevention, "no matter how old they are," Goldberg said. "For women who fall outside those categories, there are certainly recommendations in the women's guidelines that aspirin for women over age 65 does prevent a first heart attack and stroke, and for the rest of the women, until we have more research, aspirin should be used according to her level of risk, her age, and her doctor's recommendations."
While interesting, Yerman et al's study does not actually provide any new information that should alter clinical practice, Goldberg points out. "This study raises questions about aspirin in women, but it doesn't answer the questions about whether there are physiologic differences."
Source
Yerman T, Gan WQ, Sin DD. The influence of gender on the effects of aspirin in preventing myocardial infarction. BMC Med. 2007;5:29. Published online October 18, 2007.