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Aspirin for the heart is more effective in men than women, reported three newspapers (22 October 2007).The newspapers accurately reported the conclusions from a systematic review, the findings of which should be treated with caution.

Aspirin for the heart is more effective in men than women reported three newspapers, 22 October 2007, (1-3). Two of the newspapers (1,2) reported that trials that predominantly recruited men demonstrated the largest reduction in risk in non-fatal heart attacks, while trials that predominantly recruited women did not demonstrate a significant reduction in risk in non-fatal heart attacks.
The newspaper reports were based on a systematic review of 23 randomised, placebo-controlled trials, involving 113,494 patients, and aspirin at doses of 75 to 1,500mg per day (4). Overall, aspirin reduced the risk of non-fatal heart attack, but not fatal heart attacks, when compared to placebo. A proportion of the variation in the results (27%) was explained by gender. Trials that predominantly recruited men demonstrated the largest reduction in risk in non-fatal heart attacks (28%). Trials that predominantly recruited women demonstrated a reduction in risk in non-fatal heart attacks (13%), but this was not statistically significant. A similar pattern was seen when both fatal and non-fatal heart attacks were considered together (37% risk reduction in trials that recruited only men versus 14% in trials that predominantly recruited women).
The newspapers were generally accurate in their reporting of the review's conclusions. However, these conclusions should be interpreted with caution. The reviewers specifically looked at the whether gender affected the effectiveness of aspirin in prevention of heart attacks, but there are several other factors that could contribute to the variation.

Evaluation of the evidence base for the influence of gender on the efficacy of aspirin therapy for prevention of myocardial infarction.

Where does the evidence come from?

A systematic review conducted by Doctor Don Sin and colleagues from the University of British Columbia, and the James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research, St. Paul's Hospital, Vancouver, British Columbia, Canada. The review was supported ICEBERGS (Interdisciplinary Capacity Enhancement: Bridging Excellence in Respiratory Disease and Gender Studies), which is funded by the Canadian Institutes of Health Research, the Canadian Lung Association, and the Heart and Stroke Foundation of Canada.

What were the authors' objectives?

To investigate whether gender might play a role in the variation of aspirin efficacy found in primary and secondary myocardial infarction prevention trials.

What was the nature of the evidence?

This was a systematic review of 23 randomised placebo-controlled trials, involving 113,494 participants, assessing the risk of myocardial infarction whilst taking aspirin as a preventive measure. The review included trials published in English between 1966 and October 2006. Only trials deemed to have acceptable methodological quality were included in the review. The trials included a range of different populations from healthy women and healthy male physicians to patients with chronic stable or unstable angina, hypertension, cerebral infarction, minor or major stroke, non-rheumatic atrial fibrillation, constant or intermittent atrial fibrillation, at least one reversible cerebral ischemic attack, recovered myocardial infarction, high risk of cardiovascular disease, and unstable coronary artery disease. Where reported, the mean age of the trial participants ranged between 52 and 73 years, and the prevalence of current smokers varied from 11% to 60%. The main outcome was myocardial infarction (fatal and non-fatal). Separate analyses were performed for each outcome; in addition, trials were also divided into three groups based on the percentage of male participants included in each trial (0-66%, 70-89%, 100%).

What interventions were examined in the research?

Daily aspirin, dosages ranging from 75 mg to 1,500 per day, compared with placebo supplements. Follow-up ranged from 12 months to ten years.

What were the findings?

A significant reduction in the risk of non-fatal myocardial infarction was found in favour of aspirin when compared to placebo. There was no significant reduction in the risk of fatal myocardial infarction.

Trials that predominantly recruited men demonstrated the largest reduction in risk of non-fatal heart attacks (38%). Trials that predominantly recruited women demonstrated a smaller reduction in risk of non-fatal heart attacks (13%), but this was not statistically significant. When both fatal and non-fatal myocardial infarction were considered together a significant reduction in risk was found in both trials that recruited only men (37%) and in trials that predominantly recruited women (14%).

What were the authors' conclusions?

That gender accounts for a large proportion of the variability of the efficacy of aspirin in reducing myocardial infarction rates supporting the idea that women might be less responsive to aspirin therapy than men.

How reliable are the conclusions?

The literature search was restricted by language, raising the possibility of publication bias. Data extraction was performed separately by two reviewers but it was unclear whether study selection and quality assessment were also conducted this way which may have introduced errors into the process. There was considerable variation in the type of participants included in the trials, study design, and intervention which may have affected the results. It is also important to note that, as the authors themselves state, they were not able to determine the influence of other important factors such as co-morbidities that might affect the presented results. As a consequence of these considerations the conclusions should be interpreted with caution.

Systematic reviews

Information staff at CRD searched for systematic reviews relevant to this topic. Systematic reviews are valuable sources of evidence as they locate, appraise and synthesize all available evidence on a particular topic.

There were no related systematic reviews identified on the Cochrane Database of Systematic Reviews (CDSR), however there was one on the Database of Abstracts of Reviews of Effects (DARE) (5).

References and resources

1. Aspirin is good for the heart...if you're a man. Daily Express, 22 October 2007, p9.

2. Aspirin is a 'man only fix'. The Sun, 22 October 2007, p.17.

3. Aspirin 'best for men'. The Times, 22 October 2007, p.2.

4. Yerman T, Gan WQ, Sin DD. The influence of gender on the effects of aspirin in preventing myocardial infarction. BMC Medicine 2007;5:29.

5. Berger JS, Roncaglioni MC, Avanzini F, Pangrazzi I, Tognoni G, Brown DL. Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials. JAMA 2006;295(3):306-13. [DARE Abstract]