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Aspirin Less Effective for Women for MI Prevention

Oct 23, 2007

Aspirin does not prevent heart attack for women to the same extent that it does for men, researchers affirmed.

Results of a meta-analysis showed that trials that included predominantly men showed the largest risk reduction in nonfatal MI (38%), whereas those with predominately women showed no significant benefit


No significant effect in prevention of fatal MI was seen regardless of gender, reported Don D. Sin, M.D., of the University of British Columbia and St. Paul’s Hospital here, and colleagues, online in the journal BMC Medicine.

"Our findings in the context of the emerging literature regarding possible aspirin resistance in women suggest that clinicians should be cautious in prescribing aspirin in women especially for primary prevention," they wrote.

Aspirin reduces the risk of MI by about 25% on average, but trials have shown considerable variation in the effect sizes — from zero to 50% compared with placebo — the investigators said.

Their meta-analysis suggested more than a quarter of the variation may reflect lower aspirin response among women.
However, "this doesn’t change anything that we’ve already known," said Nieca Goldberg, M.D., of Lenox Hill Hospital in New York and a spokesperson for the American Heart Association in a comment. The lack of benefit for women who are "healthy and young and doing everything right" has been known from the Women’s Health Study since 2005, she said.

"The American Heart Association has been really clear in the women’s guidelines that aspirin recommendations are based on very specific cases," she said. These include primary prevention of a first MI for women over age 65 and men over 45 and in secondary prevention regardless of age or gender.

For primary prevention in younger women, the decision needs to be based on individual cardiovascular risk rather than a blanket recommendation for or against based on gender, Dr. Goldberg said.

The researchers conducted a systematic review of randomized placebo-controlled clinical trials published from 1966 through October 2006 that examined the efficacy of aspirin therapy for primary cardiovascular prevention or when taken as a pain reliever. They found 23 trials for meta-analysis with a pooled total of 113,494 participants, 49.3% of whom were men.

All but two of the trials reported on non-fatal MI outcomes, 15 reported on fatal MI, and 17 reported on both. Daily aspirin dosage ranged from 75 mg to 1,500 mg, and patients were followed for one to 10 years.  At baseline, the average age of trial participants ranged from 52 to 73, and 11% to 60% of participants were current smokers.

Aspirin significantly reduced combined risk of MI overall (RR 0.79, 95% CI 0.72 to 0.87, p<0.001).

It was effective in reducing risk of nonfatal MI with only a trend for lower fatal MI rates compared with placebo.
The proportion of men and women in each trial accounted for 27% of the variation between trials in the effectiveness of aspirin in reducing nonfatal MI (p=0.017), but did not significantly impact fatal MI (p=0.514) or the combined end point of fatal and nonfatal MI (p=0.065).

Division of the trials into tertile groups based on the gender mix suggested that men benefited from aspirin therapy whereas women did not. The findings were:

  • Trials with exclusively male participants showed the biggest benefit from aspirin in preventing nonfatal MI.
  • Trials with 70% to 89% men showed a smaller, but still significant, benefit from aspirin against nonfatal MI.
  • Those with 66% or fewer men showed no significant reduction in nonfatal MI risk with aspirin.

The findings were similar for the combined endpoint of non-fatal and fatal MI, the researchers said.
One reason they suggested for the gender difference may be aspirin resistance, which has been shown in other studies to be 2.3 to 2.5 times more common among women than men.

"Moreover, women who develop atherosclerosis tend to be older, have more co-morbid conditions and more extensive disease at the time of diagnosis, which might also interfere with the actions of aspirin," Dr. Sin’s group wrote.
Clinical studies are needed to specifically evaluate sex-specific benefits from other anti-platelet agents compared with aspirin, they concluded.

Yerman T, et al "The influence of gender on the effects of aspirin in preventing myocardial infarction" BMC Med 2007; doi:10.1186/1741-7015-5-29.


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