Abstract 4339586: Aspirin Versus P2Y12 Inhibitors as Monotherapy for Secondary Prevention in Coronary Artery Disease: A Systematic Review and Meta-analysis

Background: Coronary artery disease (CAD) is a leading cause of global morbidity and mortality. While acetylsalicylic acid (ASA) has long been the cornerstone of antiplatelet therapy, P2Y12 inhibitors such as clopidogrel and ticagrelor have emerged as alternatives. However, optimal monotherapy remains unclear. Objective: To compare the efficacy and safety of ASA versus P2Y12 inhibitors as monotherapy for secondary prevention in patients with established CAD. Methods: A rapid systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. Eligible trials compared ASA monotherapy with clopidogrel, ticagrelor, or prasugrel monotherapy in adult CAD patients. Outcomes included all-cause mortality, myocardial infarction (MI), stroke, and major bleeding. Two independent reviewers conducted study selection, data extraction, and quality assessment. Risk of bias was assessed using RoB 2, and certainty of evidence was evaluated with GRADE. Results: Five RCTs were included: two comparing ASA to clopidogrel, and three to ticagrelor. Regarding efficacy outcomes, no significant differences were observed. For ASA versus clopidogrel, the relative risk (RR) for the composite outcome of all-cause mortality, MI, and stroke was 0.86 (95% CI: 0.64–1.17). For ASA versus ticagrelor, the RR was 0.95 (95% CI: 0.76–1.18). As for the safety outcome, the HOST-EXAM trial showed a lower risk of major bleeding with clopidogrel versus ASA (HR 0.63; 95% CI: 0.41–0.97). In the comparison between ASA and ticagrelor, the GLOBAL LEADERS study was excluded from the main meta-analysis due to high risk of bias and was included only in sensitivity analyses. No direct comparisons between ASA and prasugrel were identified. According to the RoB 2 tool, two studies had low risk of bias, two had some concerns, and one was judged to have high risk of bias. Overall, evidence certainty ranged from low to very low due to imprecision, short follow-up durations, and methodological limitations. Conclusions: There was no significant difference among ASA, clopidogrel, and ticagrelor in the prevention of major cardiovascular outcomes in patients with established CAD. While clopidogrel showed a lower risk of major bleeding in one trial (HOST-EXAM), the wide confidence interval raises uncertainty about the clinical relevance of this finding. These results highlight the need for well-designed randomized trials with longer follow-up and improved methodological quality to inform future recommendations.