Effect of aspirin dose on mortality and cardiovascular events in people with diabetes: a meta-analysis.

Objectives: Pharmacologic evidence suggests adequate antiplatelet activity in diabetic patients requires >100 mg aspirin daily, yet recent trials have used ≤100 mg daily. This meta-analysis explored the relationship between aspirin dose and prevention of cardiovascular events.

Data Sources: Six electronic databases were searched using database-appropriate terms for aspirin, diabetes, and comparative study from inception until February 2010.

Review Methods: Randomized controlled trials and cohort studies comparing aspirin to no antiplatelet therapy were included if they reported cardiovascular events as pre-specified outcomes, aspirin dose, and number of diabetic patients. Studies were stratified by daily aspirin dose (≤100 mg; 101-325 mg; >325 mg) and pooled risk ratios (RR) were calculated using random effects models. All-cause mortality was the primary outcome of interest. Cardiovascular-related mortality, myocardial infarction, and stroke were secondary outcomes.

Results: Data for diabetic patients were available from 21 studies (n = 17,522). Overall, 1,172 (15.4%) of 7,592 aspirin users and 1,520 (18.4%) of 8,269 controls died (p = 0.31). The pooled RRs were 0.89 (95% CI: 0.72-1.10; p = 0.27) from 13 studies using ≤100 mg (I(2) = 64%); 0.89 (95% CI: 0.61-1.30; p = 0.55) from four studies using 101-325 mg (I(2) = 83%); and 0.96 (95% CI: 0.85-1.08; p = 0.50) from eight studies using >325 mg (I(2) = 0%). Aspirin use was associated with a significantly lower risk of mortality (RR: 0.82; 95% CI: 0.69-0.98; p = 0.03) in 13 secondary prevention studies (I(2) = 27%), whereas aspirin use in seven primary prevention studies (I(2) = 0%) was not (RR: 1.01; 95% CI 0.85-1.19; p = 0.94). A substantial amount of heterogeneity was observed amongst studies in all outcomes. Although inclusion of cohort studies was a major source of heterogeneity, stratification by study design did not reveal a significant dose-response relationship.

Conclusions/interpretation: This summary of available data does not support an aspirin dose-response effect for prevention of cardiovascular events in diabetic patients. However, the systematic review identified an important gap in randomized controlled trial evidence for using 101-325 mg aspirin daily in diabetes.