Long-term antiplatelet monotherapy remains a cornerstone of secondary prevention in CAD, yet the optimal agent remains uncertain. A rapid systematic review and meta-analysis published in Circulation evaluated whether ASA or P2Y12 inhibitor monotherapy provides superior efficacy or safety in patients with established CAD.

The analysis included 5 randomized controlled trials comparing ASA monotherapy with clopidogrel or ticagrelor monotherapy in adults with CAD. Two trials evaluated ASA versus clopidogrel, and three evaluated ASA versus ticagrelor. Outcomes included all-cause mortality, myocardial infarction, stroke, and major bleeding. Risk of bias was assessed using RoB 2, and certainty of evidence was graded using GRADE.
For the composite outcome of all-cause mortality, myocardial infarction, and stroke, no significant differences were observed. The relative risk was 0.86 (95% confidence interval [CI] 0.64–1.17) for clopidogrel versus ASA and 0.95 (95% CI 0.76–1.18) for ticagrelor versus ASA. No randomized trials directly compared ASA with prasugrel.

Regarding safety, the HOST-EXAM trial reported a lower risk of major bleeding with clopidogrel compared with ASA (hazard ratio 0.63; 95% CI 0.41-0.97). The GLOBAL LEADERS trial was excluded from the primary meta-analysis because of high risk of bias and was included only in sensitivity analyses. Across studies, two trials had low risk of bias, two had some concerns, and one had high risk of bias. Overall certainty of evidence ranged from low to very low.

These findings demonstrate no clear efficacy advantage of ASA, clopidogrel, or ticagrelor monotherapy for secondary prevention in CAD. Although clopidogrel showed lower bleeding risk in one trial, uncertainty remains due to wide confidence intervals and study limitations. Well-designed randomized trials with longer follow-up are needed to inform future antiplatelet recommendations.