Aspirin prophylaxis in patients at low risk for cardiovascular disease: A systematic review of all-cause mortality
- OBJECTIVE: We investigated whether aspirin reduces all-cause mortality in low-risk patients.
- STUDY DESIGN: We systematically reviewed studies of aspirin for primary prevention to measure total mortality. We included all clinical trials, cohort studies, and case control studies that assessed primary prevention, included low-risk subjects, and measured total mortality. The quality of studies was evaluated with a standard scale.
- DATA SOURCES: MEDLINE, the Cochrane Library, and the Internet were systematically searched for studies with the key terms primary, prevention, aspirin, myocardial infarction, stroke, and mortality. Reference lists of identified trials and reviews also were examined.
- POPULATION: Active members in the Indiana Academy of Family Physicians 2000–2001 membership database (N = 1328).
- OUTCOMES MEASURED: Primary outcomes were myocardial infarction, stroke, and mortality.
- RESULTS: Three primary prevention studies met our criteria. Two clinical trials, the United States Physicians Health Study and British Doctors Study, demonstrated no significant decrease in mortality in the aspirin group alone or when results from the 2 studies were combined. The United States Physicians Health Study showed a lower rate of myocardial infarction (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.47–0.71). In the Nurses Health Study, a cohort study, taking aspirin at any dose was associated with higher rates of myocardial infarction (OR, 2.34; CI, 1.92–2.86), stroke (OR, 1.84; CI, 1.39–2.44), and all-cause mortality (OR, 1.83; CI, 1.57–2.14).
- CONCLUSIONS: There is currently no evidence to recommend for or against the use of aspirin to decrease mortality in low-risk individuals.
There are a number of limitations to this study. There were no strictly low-risk studies of aspirin for primary prevention of cardiovascular mortality, and there was a paucity of studies that included low-risk subjects. Because the studies analyzed did not include only low-risk subjects, the results may not apply to all low-risk patients. The BDS did not include a placebo and was not blinded. Although not statistically significant, the ORs tended toward a protective effect for aspirin in the 2 randomized trials. The large difference in mortality between those 2 trials remains unexplained. The NHS was the only study to include women, and it was a cohort study, which is subject to selection and reporting biases. Therefore, aspirin users may have been at higher mortality risk due to smoking, obesity, or other illness, thus rendering the association between aspirin and higher mortality meaningless.
Many studies have shown significant side effects of aspirin, including epistaxis, peptic ulcer disease, gastrointestinal bleeds, and hemorrhagic stroke.15,20-22,27-32 In the BDS, 17% more subjects in the aspirin group developed peptic ulcer disease, and 19% stopped treatment during the first year secondary to gastrointestinal complaints.21
In conclusion, there is currently no evidence to recommend for or against the use of aspirin in low-risk individuals to decrease mortality. There may be other reasons to take aspirin prophylactically such as to reduce myocardial infarction or colon cancer. However, these benefits have not been established in a low-risk population. Health care providers should ask all patients whether they are taking aspirin and evaluate the risk-benefit ratio before recommending it.
