P2Y12 Inhibitors for Non–ST-Segment Elevation Acute Coronary Syndrome: A Systematic Review and Network Meta-Analysis

Background: For patients with non–ST-segment elevation acute coronary syndrome (NSTE-ACS), prasugrel was recommended over ticagrelor in a recent randomized controlled trial, although more data are needed on the rationale. Here, the effects of P2Y12 inhibitors on ischemic and bleeding events in patients with NSTE-ACS were investigated. Methods: Clinical trials that enrolled patients with NSTE-ACS were included, relevant data were extracted, and a network meta-analysis was performed. Results: This study included 37,268 patients with NSTE-ACS from 11 studies. There was no significant dif-ference between prasugrel and ticagrelor for any end point, although prasugrel had a higher likelihood of event reduction than ticagrelor for all end points except cardiovascular death. Compared with clopidogrel, prasugrel was associated with decreased risks of major adverse cardiovascular events (MACE) (hazard ratio [HR], 0.84; 95% CI, 0.71-0.99) and myocardial infarction (HR, 0.82; 95% CI, 0.68-0.99) but not an increased risk of major bleeding (HR, 1.30; 95% CI, 0.97-1.74). Similarly, compared with clopidogrel, ticagrelor was associated with a reduced risk of cardiovascular death (HR, 0.79; 95% CI, 0.66-0.94) and an increased risk of major bleeding (HR, 1.33; 95% CI, 1.00-1.77; P =.049). For the primary efficacy end point (MACE), prasugrel showed the highest likelihood of event reduction (P =.97) and was superior to ticagrelor (P =.29) and clopi-dogrel (P =.24). Conclusion: Prasugrel and ticagrelor had comparable risks for every end point, although prasugrel had the highest probability of being the best treatment for reducing the primary efficacy end point. This study high-lights the need for further studies to investigate optimal P2Y12 inhibitor selection in patients with NSTE-ACS.