Background: ASA is the only antiplatelet agent with a Class I recommendation for long-term prevention of cardiovascular events in patients with coronary artery disease (CAD). There is inconsistent evidence on how it compares with alternative antiplatelet agents.

Methods: We conducted a patient-level metaanalysis of randomized trials comparing P2Y12 inhibitor monotherapy vs ASA monotherapy for the prevention of cardiovascular events in patients with established CAD. The primary outcome was the composite of cardiovascular death, myocardial infarction, and stroke. Prespecified key secondary outcomes were major bleeding and net adverse clinical events (the composite of the primary outcome and major bleeding). Data were pooled in a 1-step meta-analysis.

Results: Patient-level data were obtained from 7 trials. Overall, 24,325 participants were available for analysis, including 12,178 patients assigned to receive P2Y12 inhibitor monotherapy (clopidogrel in 7,545 [62.0%], ticagrelor in 4,633 [38.0%]) and 12,147 assigned to receive ASA. Risk of the primary outcome was lower with P2Y12 inhibitor monotherapy compared with ASA over 2 years (HR: 0.88; 95% CI: 0.79-0.97; P=0.012), mainly owing to less myocardial infarction (HR: 0.77; 95% CI: 0.66-0.90; P<0.001). Major bleeding was similar (HR: 0.87; 95% CI: 0.70-1.09; P=0.23) and net adverse clinical events were lower (HR: 0.89; 95% CI: 0.81-0.98; P=0.020) with P2Y12 inhibitors. The treatment effect was consistent across prespecified subgroups and types of P2Y12 inhibitors.