Comparative Efficacy and Safety of Oral P2Y 12 Inhibitors in Acute Coronary Syndrome

Abstract

Background: New randomized controlled trials (RCTs) have become available on oral P2Y₁₂ inhibitors in acute coronary syndrome (ACS). We aimed to evaluate current evidence comparing the efficacy and safety profile of prasugrel, ticagrelor and clopidogrel in ACS by a meta-analysis of RCTs. Methods: We performed a network meta-analysis and direct pairwise comparison analysis of efficacy and safety outcomes from twelve RCTs including a total of 52,816 patients with ACS. Results: Compared with clopidogrel, ticagrelor significantly reduced cardiovascular mortality (hazard ratio(HR), 0.82 [95% confidence interval(CI), 0.72-0.92]) and all-cause mortality (HR, 0.83 [95% CI, 0.75-0.92]), whereas there was no statistically significant mortality reduction with prasugrel (HR, 0.90 [95% CI, 0.80-1.01] and HR, 0.92 [95% CI, 0.84-1.02], respectively). Compared with each other there were no significant differences in mortality (HR prasugrel vs ticagrelor, 1.10 [95% CI, 0.94-1.29] and 1.12 [95% CI, 0.98-1.28]). Compared with clopidogrel, prasugrel reduced myocardial infarction (HR, 0.81 [95% CI, 0.67-0.98]), whereas ticagrelor showed no risk reduction (HR, 0.97 [95% CI, 0.78-1.22]). Differences between prasugrel and ticagrelor were not statistically significant. Stent thrombosis risk was significantly reduced by both ticagrelor and prasugrel vs clopidogrel (28-50% range of reduction). Compared with clopidogrel, both prasugrel (HR, 1.26 [95% CI, 1.01-1.56]) and ticagrelor (HR, 1.27 [95% CI, 1.04-1.55]) significantly increased major bleeding. There were no significant differences between prasugrel and ticagrelor for all outcomes explored. Conclusions:Prasugrel and ticagrelor reduced ischemic events and increased bleeding in comparison to clopidogrel. A significant mortality reduction was observed with ticagrelor only. There was no efficacy and safety difference between prasugrel and ticagrelor. PROSPERO ID: CRD42019155648