P2Y12 inhibitors in patients with non-ST-segment elevation acute coronary syndrome: systematic review and network meta-analysis of randomized trials

Background Based on a recent randomized control trial (RCT), prasugrel is recommended in preference to ticagrelor for patients with non-ST-segment elevation ACS (NSTE-ACS), however, limited data exists. Objectives We aimed to investigate the effect of P2Y12 inhibitors on ischemic and bleeding events in NSTE-ACS patients. Methods Clinical trials enrolling NSTE-ACS patients were identified and relevant data was extracted. We performed a network meta-analysis on efficacy and safety outcomes. Results Our study including a total of 37, 268 patients with NSTE-ACS from 11 RCTs. Prasugrel decreased major adverse cardiovascular events (MACE) when compared to clopidogrel (Hazard ratio (HR): 0.84; 95% confidence interval (CI) [0.71–0.99]). For MACE, prasugrel showed the highest likelihood of event reduction (P-score=0.97) in comparison to ticagrelor (P-score=0.29) and clopidogrel (P-score=0.24). Prasugrel decreased myocardial infarction (HR: 0.82; 95% CI [0.68–0.99]) but increased major bleeding without statistical significance (HR: 1.30; 95% CI [0.97–1.74]) when compared to clopidogrel. Ticagrelor reduced cardiovascular death (HR: 0.79; 95% CI [0.66–0.94]) but increased major bleeding (HR: 1.33; 95% CI [1.00–1.77], p=0.049) in comparison to clopidogrel. There was no significant difference between prasugrel and ticagrelor for each endpoint, but prasugrel had higher likelihood of event reduction than ticagrelor for all endpoints except cardiovascular death. Conclusions Prasugrel and ticagrelor had comparable risk for each endpoint, but prasugrel had the highest probability being the best treatment in reducing the primary endpoint. This study highlights the need for further large-scale RCTs to investigate the optimal P2Y12 inhibitor selection in NSTE-ACS patients. Funding Acknowledgement Type of funding sources: None.