Comparative efficacy and safety of oral P2Y12 inhibitors after non-ST-elevation acute coronary syndromes: a network meta-analysis

Background Currently, potent P2Y12 inhibition with the use of prasugrel or ticagrelor is the mainstay of treatment after an acute coronary syndrome (ACS). The 2020 European Society of Cardiology (ESC) Guidelines recommend the use of prasugrel over ticagrelor in patients with non-ST-elevation ACS (NSTE-ACS) intended to receive invasive management (class IIa recommendation), however there are contradictory views regarding this recommendation. Aim To compare oral P2Y12 inhibitors in NSTE-ACS in terms of efficacy and safety with a focus on patients intended to proceed to invasive management. Methods We systematically searched PubMed, Cochrane Central Register of Controlled Trials and Web of Science to identify studies that compared different oral P2Y12 inhibitors (clopidogrel, prasugrel and ticagrelor) in patients with NSTE-ACS. Efficacy outcomes included the major adverse cardiovascular events outcome and safety outcomes included minor and major bleedings. We performed a frequentist network meta-analysis. Results Nine studies (n=35 441 patients) were included in the systematic review. There was no difference between prasugrel and ticagrelor in the composite cardiovascular end point (prasugrel vs ticagrelor HR=0.80, 95% CI=0.61 to 1.06) in all patients with NSTE-ACS. In patients intended to receive invasive management, prasugrel resulted in a reduction of the composite cardiovascular end point both versus clopidogrel (HR=0.76, 95% CI=0.61 to 0.95) and ticagrelor (HR=0.74, 95% CI=0.56 to 0.98). Inconsistency was moderate and non-significant (I2=27%, total Q p=0.2). Prasugrel ranked as the most efficient treatment in the composite cardiovascular efficacy outcome, all-cause death, myocardial infarction and definite stent thrombosis, while clopidogrel ranked as safest in the bleeding outcomes. Conclusion In patients with NSTE-ACS intended to receive invasive management, an antiplatelet strategy based on prasugrel is more efficient than a similar strategy based on ticagrelor on a moderate level of evidence. This analysis supports the current recommendations by the ESC guidelines.