Choosing the most effective and safest P2Y12 Inhibitor for use in >70-year-old acute coronary syndrome patients: a network meta-analysis

Abstract Background Acute coronary syndrome (ACS) represents a significant health burden, especially in elderly patients. Antiplatelet therapy forms the cornerstone of medical treatment for ACS, prasugrel and ticagrelor are preferred for their rapid action and proven efficacy. Despite their benefits, the comparative effectiveness and safety of prasugrel, ticagrelor, and clopidogrel, especially in elderly ACS patients, represents a true gap of knowledge. Aim This study aims to compare the efficacy and safety of prasugrel, ticagrelor, and clopidogrel in elderly patients with ACS, focusing on outcomes such as major adverse cardiovascular events (MACE), stroke, major or moderate bleeding, myocardial infarction (MI), all-cause mortality, cardiac mortality, revascularization, and stent thrombosis. Methods We conducted a comprehensive literature search across PubMed, Web of Science, Cochrane, Scopus, and ClinicalTrials.gov. Thirty-seven studies were included in our network meta-analysis (NMA), with data extracted on various outcomes. Data reported as relative risks (RRs) with 95% confidence intervals. Results Our NWM revealed that there is no significant difference in the incidence of MACE between prasugrel and ticagrelor or clopidogrel (RR 0.91 [0.67, 1.25] and RR 0.86 [0.64, 1.15], respectively). Stroke outcomes also showed no significant difference (RR 0.88 [0.60, 1.28] for prasugrel vs. ticagrelor; RR 0.73 [0.52, 1.02] for prasugrel vs. clopidogrel). Ticagrelor compared to clopidogrel significantly increased the risk of major or moderate bleeding (RR 1.23 [1.08, 1.39]). Significantly decreased risks of cardiac mortality were found for prasugrel and ticagrelor compared to clopidogrel (RR 0.88 [0.78, 0.98] and OR 0.81 [0.73, 0.90], respectively). Prasugrel significantly reduced the risk of revascularization compared to ticagrelor and clopidogrel (RR 0.57 [0.42, 0.78] and RR 0.75 [0.64, 0.88], respectively). For stent thrombosis, prasugrel and ticagrelor both showed significantly decreased risks compared to clopidogrel (RR 0.71 [0.55, 0.92] and RR 0.76 [0.62, 0.93], respectively). for MI, no significant difference was observed between prasugrel and ticagrelor (RR 0.88 [CI 0.64-1.20]), prasugrel and clopidogrel (RR 0.81 [0.60-1.09]), or ticagrelor and clopidogrel (RR 0.92 [CI 0.73-1.16]). Similarly, all-cause mortality rates did not significantly differ, with an RR of 0.93 [0.68-1.27] for prasugrel vs. ticagrelor, and an RR of 0.80 [0.61-1.06] for prasugrel vs. clopidogrel. Conclusion Our NMA suggests that while there are no significant differences among prasugrel, ticagrelor, and clopidogrel in reducing the risk of MACE, stroke, MI, and all-cause mortality in elderly ACS patients, ticagrelor may increase the risk of bleeding. Prasugrel and ticagrelor offer advantages in reducing cardiac mortality, revascularization, and stent thrombosis.