Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials

Overview

The authors combined information from six key randomized controlled trials between 1966 and 2005 to determine the overall benefits and harms of aspirin use in persons with no known heart disease. These studies all included information on important heart disease and stroke outcomes experienced by trial participants. The authors examined gender differences in the outcomes for those taking aspirin. They found that aspirin benefits differed substantially by gender; aspirin reduced the risk of heart attack in men and the risk of stroke in women.

Methodology

This study was a meta-analysis combining information from six key randomized controlled trials. The studies included were published between 1966 and 2005. The six trials included a total of 95,456 individuals. Three trials included only men, one only women, and two both genders. The authors sought to examine differences by gender in outcomes experienced by those taking aspirin compared to those taking placebo. Aspirin dose varied from 100 mg every other day to 500 mg per day.

Results

  • Among men in these studies, taking aspirin resulted in a 14% reduction in all cardiovascular events and a 32% reduction in the risk of heart attack.

  • Among women, taking aspirin resulted in a 12% reduction in all cardiovascular events and a 17% reduction in all strokes.

  • The risk of strokes where blood flow to the brain is interrupted (ischemic strokes) was reduced by 24% in women, but this benefit was not as great when all types of strokes were counted (including hemorrhagic strokes where there is bleeding into the brain).

  • Men taking aspirin were 69% more likely to have hemorrhagic strokes.

  • Across these studies, aspirin did not change a woman’s risk of having a heart attack nor did it change a man’s risk of having a stroke.

  • For both men and women, aspirin failed to make a difference in the risk of cardiovascular disease deaths.

  • Aspirin treatment increased the risk of bleeding similarly in women (a 68% increase) and men (a 72% increase).

Conclusions

  • Aspirin does not produce clear-cut reduction in the composite outcome of cardiovascular disease events. For the primary outcome of the composite cardiovascular disease events there was only a modest statistically significant reduction in events for those taking aspirin vs. placebo (a 14% decrease in men and a 12% decrease for women).

  • The beneficial and harmful impacts of aspirin differ substantially by gender. There were dramatic differences in individual cardiac events by gender. For example, aspirin was shown to reduce the risk of heart attack in men and the risk of stroke in women. This information should be communicated to patients but, in both cases, one has to gauge that benefit against the harm involved.

  • There is a need to carefully select populations for aspirin therapy. The authors indicate that greater absolute benefits would likely accrue with aspirin use in populations at higher initial risk of cardiovascular disease. Their minimal clinical guidance is to consider both benefits and harms in selecting patients for the use of aspirin in primary prevention.