Ischaemic and bleeding complications with new, compared to standard, ADP-antagonist regimens in acute coronary syndromes: A meta-analysis of randomized trials

Background: Platelets play a pivotal role in the pathogenesis of acute coronary syndromes (ACS) and their inhibition remains a mainstay therapy in this setting. We aimed to perform a meta-analysis of randomized trials to evaluate the benefits of new oral antiplatelet regimens to block platelet ADP-receptors compared to standard-dose clopidogrel (300 mg loading dose followed by 75 mg/daily). Methods: We obtained results from all randomized trials enrolling patients with ACS. Primary endpoint was mortality. Secondary endpoints were myocardial infarction and definite in-stent thrombosis. Safety endpoint was the risk of major bleeding complications. We prespecified subanalyses according to new antiplatelet drugs (prasugrel/ticagrelor), high-dose clopidogrel (600 mg) and patients undergoing percutaneous coronary intervention. Results: A total of seven randomized trials were finally included in the meta-analysis (n = 58 591). We observed a significant reduction in mortality (2.9% vs. 3.4%, OR = 0.87, 95% CI 0.79-0.95, P = 0.002), recurrent myocardial infarction (4.2% vs. 5.2%, OR = 0.80, 95% CI 0.74-0.87, P < 0.0001), definite in-stent thrombosis (0.9% vs. 1.7%, OR = 0.52, 95% CI 0.43-0.63, P < 0.0001). The benefits in mortality and reinfarction were driven by the treatment with prasugrel or ticagrelor, without a significant difference in terms of major bleeding complications as compared to standarddose clopidogrel (5% vs. 4.7%, OR = 1.06 95% CI 0.96-1.17, P = 0.25). Conclusions: This meta-analysis showed that new oral antiplatelet regimens are associated with a significant reduction in mortality, reinfarction and in-stent thrombosis in ACS patients without an overall increase of major bleeding when treated with new antiplatelet drugs.