Abstract
Previous studies and meta-analyses have assessed optimal P2Y12 inhibitors following acute coronary syndrome in overall trial cohorts. However, there are insufficient data for the elderly cohort who are prone to high bleeding and ischemic events. We aimed to assess the optimal P2Y12 inhibitor therapy for older patients.
PubMed, CENTRAL, and ClinicalTrials.gov databases were searched from inception through July 2020 to identify randomized controlled trials and propensity-matched observational studies including older patients (aged ≥ 65 years) that reported study-defined major adverse cardiovascular events (MACE) or major bleeding events. Outcomes at the mid-term follow-up were pooled to conduct a frequentist network meta-analysis.
Fourteen studies involving 12,953 older patients were included in our analysis. No significant difference was observed with MACE when all three P2Y12 inhibitors were compared with each other. Compared with clopidogrel, ticagrelor significantly increased the risk of major bleeding (risk ratio 1.35, 95% confidence interval 1.10-1.67) while prasugrel did not (risk ratio 1.02, 95% confidence interval 0.67-1.57). A sensitivity analysis of only randomized controlled trials yielded similar results for both MACE and major bleeding. The P score displayed prasugrel (0.5871) as the best treatment for MACE, while clopidogrel (0.7701) was the best P2Y12 inhibitor to decrease the risk of major bleeding. Ticagrelor (0.0634) was ranked the lowest because of an increased bleeding risk.
No significant difference is observed between the three P2Y12 inhibitors in study-defined MACE. Ranking by p-score suggests prasugrel as the best P2Y12 inhibitor to reduce the risk of MACE while clopidogrel is a better alternative than ticagrelor in older patients with acute coronary syndrome to decrease the risk of major bleeding. Because of a lack of individual-patient data analysis and heterogeneity amongst studies, future studies representing older patients with acute coronary syndrome are required to strengthen evidence regarding optimal antithrombotic therapy in this cohort.