Aspirin prophylaxis in patients at low risk for cardiovascular disease: a systematic review of all-cause mortality - Original Research

Journal of Family Practice, August, 2002 by John M. Boltri, Mark R. Akerson, Robert L. Vogel

Every trial was evaluated independently by each author according to the Jadad scale. (17) Based on information in the original articles, we recalculated the odds ratios (ORs) for each study. The results of the 2 randomized trails were combined by means of the Mantel-Haenszel method for combining ORs, and StatXact 4 for Windows was used for the analysis. (18, 19) The data were used to create a forest plot of mortality. (19) The decision to combine studies of like type was made a priority.

RESULTS

MEDLINE search results for aspirin and primary prevention yielded 291 articles. Antiplatelet theraphy and primary prevention yielded 64 articles. Myocardial infarction or stroke and primary prevention yielded 514 articles. Cross-referencing aspirin, prevention, and mortality yielded 690 articles. The Cochrane Library search of antiplatelet therapy and prevention and primary yielded 17 complete reviews and 6 abstracts of systematic reviews. No additional studies published or unpublished were identified through the Internet.

Five clinical trials and 1 cohort study that evaluated aspirin for primary prevention were identified. (11, 12, 20-23) One of those, a pilot study, was excluded because it did not provide mortality data for the aspirin and placebo groups. (23) Two clinical trials, the Hypertension Optimal Treatment Trial and the Thrombosis Prevention Trial, did not include low-risk subjects. (11, 12) Although no studies were identified that included only low-risk subjects, 3 studies met our inclusion criteria. Characteristics of those 3 studies are reported in Table 1.

The US Physicians Health Study (USPHS) randomized physicians into 4 treatment groups: aspirin plus beta-carotene, aspirin plus placebo, beta-carotene plus placebo, and placebo plus placebo. (20) Both aspirin groups took 325 mg every other day. The mean age was 53.2 years. (24) Fifty percent of the participants were current or past smokers, and 9% had hypertension. Although the rate of myocardial infarction was significantly lower in the aspirin group, there was no reduction in total cardiovascular mortality. The results are reported in Table 2. More side effects were noted in the aspirin group, including gastric ulcers, gastrointestinal bleeding, hemorrhagic stroke, and other bleeding disorders. (20) No separate analysis of low-risk subjects' risk was performed.

In the British Doctors Study (BDS), 66% of patients were randomized to take aspirin once daily and 33% were to avoid aspirin. (21) More than half of the subjects were at least 60 years old. Physicians with stroke, myocardial infarction, ulcer disease, or currently taking any aspirin products were excluded. Six percent of the subjects had a history of heart disease other than myocardial infarction, 10% had hypertension, and 75% of participants were currently smoking or had a history of smoking. No significant differences were noted between groups for myocardial infarction or total mortality. By the end of the study, 44% of the aspirin group had discontinued aspirin secondary to side effects, the most common being dyspepsia. Of the control group, 2% per year started using aspirin because they developed risk factors such as vascular disease or for primary prevention. Low-risk individuals were not evaluated separately.