Efficacy and safety of newer P2Y12 inhibitors versus clopidogrel in patients with acute coronary syndrome

Abstract

Introduction: Newer P2Y12 inhibitors are more potent than clopidogrel. Whether they are safer or more efficacious in patients with acute coronary syndrome (ACS) is uncertain. We used a network meta-analysis to compare different P2Y12 inhibitors with respect to clinical outcomes. Methods: We searched for randomised controlled trials comparing clopidogrel, prasugrel, ticagrelor, or cangrelor, in combination with aspirin in patients with ACS. Those reporting major adverse cardiovascular events, bleeding events and deaths were eligible to be included. Network meta-analysis was performed using random-effects model in R. Results: Fifteen trials with altogether 69 086 patients were included. Compared with clopidogrel, prasugrel significantly reduced major adverse cardiovascular events (odds ratio [OR]=0.80, 95% confidence interval [CI]=0.66-0.98) whereas ticagrelor significantly reduced all-cause mortality (OR=0.83, 95% CI=0.71-0.95). Prasugrel and ticagrelor both lowered the risk of myocardial infarction (OR=0.79, 95% CI=0.67-0.94 and OR=0.78, 95% CI=0.63-0.97), cardiovascular mortality (OR=0.87, 95% CI=0.76-0.99 and OR=0.84, 95% CI=0.73-0.98), and stent thrombosis (OR=0.48, 95% CI=0.35-0.64 and OR=0.62, 95% CI=0.45-0.86), respectively. However, there was a significant increase in thrombolysis in myocardial infarction major bleeds (OR=1.26, 95% CI=1.02-1.55) and minor bleeds (OR=1.44, 95% CI=1.16-1.77) with prasugrel. In addition, prasugrel had fewer stent thromboses than cangrelor (OR=0.60, 95% CI=0.39-0.93) but more thrombolysis in myocardial infarction minor bleeds than ticagrelor (OR=1.42, 95% CI=1.08-1.87). No significant increase in the risk of stroke was found. Conclusion: Prasugrel and ticagrelor reduce the risk of cardiovascular events and deaths in patients with ACS when compared with clopidogrel. Cangrelor is comparable to clopidogrel. Prasugrel gives the most benefits among the newer P2Y12 inhibitors, but at the expense of an increase in bleeding. The choice of a newer P2Y12 inhibitor over clopidogrel should be made after considering the benefit-risk profile of each patient with ACS.