Graphical Abstract.

A meta-analysis of 9 randomized trials (61 623 patients) was conducted to compare P2Y₁₂ inhibitor monotherapy versus aspirin monotherapy for secondary prevention of cardiovascular events in patients with established atherosclerotic cardiovascular disease (coronary, cerebrovascular, or peripheral artery disease). The included studies had follow-up periods between 3 and 36 months. Monotherapy with P2Y₁₂ inhibitors (clopidogrel or ticagrelor) 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, all-cause mortality, or major bleeding. Subgroup analysis revealed that the reduction in MACE with P2Y₁₂ inhibitors was driven by a reduction in recurrence of the qualifying event. CI = confidence interval, P2Y12i = P2Y₁₂ inhibitor, RR = risk ratio.