P2Y12 inhibitor versus aspirin monotherapy for secondary prevention of cardiovascular events: meta-analysis of randomized trials

Eur Heart J Open. 2022 Mar 21;2(2):oeac019. doi: 10.1093/ehjopen/oeac019. eCollection 2022 Mar.

Abstract

Aim: To compare the efficacy and safety of P2Y12 inhibitor or aspirin monotherapy for secondary prevention in patients with atherosclerotic cardiovascular disease (ASCVD).

Methods and results: Medline, Embase, and Cochrane Central databases were searched to identify randomized trials comparing monotherapy with a P2Y12 inhibitor versus aspirin for secondary prevention in patients with ASCVD (cardiovascular, cerebrovascular, or peripheral artery disease). The primary outcome was major adverse cardiac events (MACE). Secondary outcomes were myocardial infarction (MI), stroke, all-cause mortality, and major bleeding. A random-effects model was used to calculate risk ratios (RR) and the corresponding 95% confidence interval (CI) and heterogeneity among studies was assessed using the Higgins I2 value. A total of 9 eligible trials (5 with clopidogrel and 4 with ticagrelor) with 61 623 patients were included in our analyses. Monotherapy with P2Y12 inhibitors significantly reduced the risk of MACE by 11% (0.89, 95% CI 0.84-0.95, I2 = 0%) and MI by 19% (0.81, 95% CI 0.71-0.92, I2 = 0%) compared with aspirin monotherapy. There was no significant difference in the risk of stroke (0.85, 95% CI 0.73-1.01), or all-cause mortality (1.01, 95% CI 0.92-1.11). There was also no significant difference in the risk of major bleeding with P2Y12 inhibitor monotherapy compared with aspirin (0.94, 95% CI 0.72-1.22, I2 = 42.6%). Results were consistent irrespective of the P2Y12 inhibitor used.

Conclusion: P2Y12 inhibitor monotherapy for secondary prevention is associated with a significant reduction in atherothrombotic events compared with aspirin alone without an increased risk of major bleeding.

Keywords: Antiplatelet agents; Aspirin; Atherosclerotic cardiovascular disease; Myocardial infarction; P2Y12 inhibitors; Stroke.