Meta-Analysis of the Relative Efficacy and Safety of Oral P2Y12 Inhibitors in Patients With Acute Coronary Syndrome

A cornerstone of medical therapy for patients with acute coronary syndrome (ACS) is dual antiplatelet therapy, which includes aspirin and a P2Y12 inhibitor. Randomized controlled trials (RCTs) have shown that prasugrel and ticagrelor are superior to clopidogrel, but none directly compared these 3 commonly used oral P2Y12 inhibitors for safety and efficacy. Therefore, we performed a Bayesian network meta-analysis of RCTs to compare the efficacies and safeties of 3 commonly used oral P2Y12 inhibitors in patients with ACS. Scientific databases and websites were searched for relevant RCTs. We included data from 9 RCTs that enrolled 106,288 patients. Clopidogrel decreased the rates of major adverse cardiac event, recurrent myocardial infarction, and all-cause mortality compared with placebo. Both ticagrelor and prasugrel decreased the rates for major adverse cardiac event and recurrent myocardial infarction compared with clopidogrel, but there was no difference between the 2. Both also decreased the stent thrombosis rate compared with clopidogrel, but prasugrel was more effective than ticagrelor. Ticagrelor use was also associated with improved all-cause and CV mortalities compared with clopidogrel. There was no difference in CV mortality or all-cause mortality between clopidogrel and prasugrel. Prasugrel use was also associated with significantly increased risk of major bleeding compared with clopidogrel but showed a nonsignificant trend toward increasing the risk of bleeding compared with ticagrelor. In treatment ranking, ticagrelor was the most efficacious, and prasugrel was the least safe. In conclusion, this meta-analysis shows that in patients with ACS, adding P2Y12 inhibitors to aspirin and other standard treatments reduces ischemic events and all-cause mortality. Among the commonly used oral P2Y12 inhibitors, ticagrelor has the best net efficacy and safety profile.