Nine RCTs were included in the review (100,076 participants). Mean follow-up duration in the included studies ranged from 3.8 to 10.1 years. Six trials were double-blinded and three trials were open label. All trials reported the process of sequence generation and concealment of allocation. Blinding of outcome assessors was adequate in all studies. Loss to follow-up rates ranged from less than 1% to 7.6%. Treatment adherence ranged from 50% to 93%. All studies used an intention-to-treat analysis.
Compared with placebo/no aspirin treatment, aspirin was associated with a marginally significant reduction in all-cause mortality (RR 0.94, 95% CI 0.88 to 1.00; nine trials) and myocardial infarction (RR 0.83, 95% CI 0.69 to 1.00; nine trials). It was associated with a significant reduction in ischaemic stroke (RR 0.86, 95% CI 0.75 to 0.98; eight RCTs) and the composite of myocardial infarction, stroke and cardiovascular death (RR 0.88, 95% CI 0.83 to 0.94; nine RCTs), but did not reduce cardiovascular mortality (RR 0.96, 95% CI, 0.84 to1.09; nine trials). Aspirin significantly increased the risk of hemorrhagic stroke (RR 1.36, 95% CI 1.01 to 1.82; eight trials), major bleeding (RR 1.66, 95% CI 1.41 to 1.95; seven trials) and gastrointestinal bleeding (RR 1.37, 95% CI 1.15 to 1.62; eight trials).
Significant heterogeneity was observed in the outcomes of myocardial infarction (I2=71%) and gastrointestinal bleeding (I2=62%). Sensitivity analyses did not materially alter the results. There was no evidence of publication bias.