(VP093) ROLE OF LOW-DOSE ASPIRIN FOR THE PRIMARY PREVENTION OF ISCHEMIC VASCULAR EVENTS: AN UPDATED SYSTEMATIC REVIEW AND META-ANALYSIS

Background: The 2010 Canadian Cardiovascular Society (CCS) Antiplatelet (ATP) Guidelines recommend against the routine use of aspirin in primary prevention of atherosclerotic cardiovascular diseases (ASCVD). Since then, several large clinical randomized controlled trials (RCTs) evaluating the role of aspirin in primary prevention have been published. In this updated systematic review and meta-analysis, we compared the effect of low-dose aspirin compared with no aspirin on ischemic and bleeding events in patients without known ASCVD.

METHODS AND RESULTS: We updated a published systematic review and meta-analysis by searching MEDLINE, Embase and CENTRAL until March 2023. In duplicate, reviewers screened references and then potentially eligible full-text articles. We included RCTs that selected patients for primary prevention of ASCVD and compared low-dose aspirin (80-160 mg) administration to no aspirin. We assessed risk of bias (RoB) using the Cochrane RoB2 tool and certainty of evidence using GRADE framework. The primary efficacy outcome was major adverse cardiovascular events (MACE defined as death, myocardial infarction, or stroke). Safety outcomes were intracranial hemorrhage (ICH) and extra-cranial major bleeding (ECMB) events. We examined risk ratios (RR) and 95% confidence intervals (CI) using a random-effects model. We performed subgroup analyses based on age, sex and presence of diabetes for MACE, major bleeding and mortality. The updated search yielded 4441 references. We found one trial (n= 5713 patients) that had not been included in the previous meta-analysis for a total of 14 RCTs (n=183,643) at overall low RoB with a median follow-up of 5 years. Compared to no aspirin, low-dose aspirin reduced MACE (RR 0.90, 95% CI 0.86-0.94, I2 = 0%; 4 fewer events per 1000 patients, high quality evidence) but with a higher risk of ICH (RR 1.33, 95% CI 1.13-1.56, I2=0%; 1 more event per 1000 patients, high quality evidence) and major bleeding (RR 1.67, 95% CI 1.36-2.06, I2=63%; 5 more events per 1000 patients, high quality evidence). There was no benefit on all-cause mortality (RR 0.97, 95% CI 0.93-1.01, I2 = 0%, high quality evidence). The results in prespecified subgroups based on age, sex and presence of diabetes were consistent with the main analysis.

Conclusion: Aspirin in primary prevention is associated with a consistent reduction in MACE, but at the expense of major bleeding events, with a neutral effect on mortality. Patient values and risk preferences, in addition to individual risk profiles, should be assessed when considering aspirin for primary prevention.