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

BackgroundSince the publication of the 2010 Canadian antiplatelet guidelines, there have been several large randomized controlled trials (RCTs) evaluating the role of aspirin (ASA) in primary prevention. We evaluated the effect of ASA compared with no ASA on ischemic and bleeding events in patients without known atherosclerotic cardiovascular diseases (ASCVD).MethodsWe updated a published systematic review and meta-analysis by searching MEDLINE, Embase and CENTRAL up to March 2023. We included randomized controlled trials (RCTs) that enrolled patients for primary prevention of ASCVD and compared ASA to no ASA. We assessed risk of bias (RoB) using the Cochrane RoB tool and certainty of evidence using GRADE criteria. The primary efficacy outcome was major adverse cardiovascular events (MACE) (death, myocardial infarction or stroke). The primary safety outcomes were intracranial hemorrhage (ICH) and extracranial major bleeding (ECMB) events. We used a random-effects model to generate pooled risk ratios (RR) and 95% confidence intervals (CI).ResultsWe included fourteen RCTs (n=167,587) at overall low RoB with a median follow-up of 5 years. Compared to no ASA, ASA reduced MACE (RR 0.90, 95% CI 0.86-0.94) with a higher risk of ICH (RR 1.33, 95% CI 1.13-1.56) and ECMB (RR 1.67, 95% CI 1.36-2.06). In pre-specified subgroups of age, sex and diabetes, effect estimates were consistent.ConclusionASA 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 for primary prevention.