Aspirin for the Primary Prevention of Vascular Ischemic Events: An Updated Systematic Review and Meta-analysis to Support Shared Decision-Making

Background: Since the publication of the 2010 Canadian antiplatelet guidelines, several large randomized controlled trials (RCTs) have evaluated the role of aspirin (ASA) use in primary prevention. We evaluated the effect of ASA use, compared with no ASA, on ischemic and bleeding events in patients without known atherosclerotic car-diovascular diseases.Methods: We updated a published systematic review and meta-analysis by searching MEDLINE, Embase, and CENTRAL for the period up to March 2023. We included RCTs that enrolled patients for primary prevention of atherosclerotic cardiovascular diseases, and compared use of ASA to no ASA. We assessed risk of bias (RoB) using the Cochrane RoB tool, and certainty of evidence using the grading recommendations, assessment, development, and evaluation (GRADE) criteria. The primary efficacy outcome was major adverse cardiovascular events (MACE) (death, myocardial infarction, or stroke). The primary safety outcomes were intracranial hemorrhage and extracranial major bleeding events. We used a random-effects model to generate pooled risk ratios (RRs) and 95% confidence intervals (CIs).Results: We included 14 RCTs (n = 167,587) at overall low RoB, with a median follow-up of 5 years. Compared to no ASA, ASA use reduced the incidence of MACE (RR 0.90, 95% CI 0.86-0.94), with a higher risk of intracranial hemorrhage (RR 1.33, 95% CI 1.13-1.56) and extra cranial major bleeding (RR 1.67, 95% CI 1.36-2.06). In prespecified subgroups of age, sex, and diabetes, effect estimates were consistent.Conclusions: ASA use in primary prevention is associated with a consistent reduction in MACE, but at the expense of major bleeding events. Patient values and preferences should be taken into account when considering ASA use for primary prevention.