Efficacy and safety of aspirin for primary prevention of cardiovascular events: a meta-analysis and trial sequential analysis of randomized controlled trials

Aims The role of aspirin in the primary prevention setting is continuously evolving. Recent randomized trials have challenged the role of aspirin in the primary prevention setting. Methods and results Electronic databases were searched for randomized trials that compared aspirin vs. placebo (or control) in subjects without established atherosclerotic disease. The primary efficacy outcome was all-cause mortality, while the primary safety outcome was major bleeding. Summary estimates were reported using a DerSimonian and Laird random effects model. A total of 11 trials with 157 248 subjects were included. At a mean follow-up of 6.6 years, aspirin was not associated with a lower incidence of all-cause mortality [risk ratio (RR) 0.98, 95% confidence interval (Cl) 0.93-1.02; P=0.30]; however, aspirin was associated with an increased incidence of major bleeding (RR 1.47, 95% CI 1.31-1.65; P < 0.0001) and intracranial haemorrhage (RR 1.33, 95% CI 1.13-1.58; P=0.001). A similar effect on all-cause mortality and major bleeding was demonstrated in diabetic and high cardiovascular risk patients (i.e. 10-year risk >7.5%). Aspirin was associated with a lower incidence of myocardial infarction (RR 0.82, 95% CI 0.71-0.94; P=0.006); however, this outcome was characterized by considerable heterogeneity (I-2 = 67%), and this effect was no longer evident upon limiting the analysis to the more recent trials. Trial sequential analysis confirmed the lack of benefit of aspirin for all-cause mortality up to a relative risk reduction of 5%. Conclusion Among adults without established cardiovascular disease, aspirin was not associated with a reduction in the incidence of all-cause mortality; however, it was associated with an increased incidence of major bleeding. The routine use of aspirin for primary prevention needs to be reconsidered.