P2Y12 Receptor Antagonists: Which One to Choose? A Systematic Review and Meta-Analysis

Background: Pharmacological properties of the currently available P2Y12 receptor antagonists differ significantly and lead to different degrees of platelets inhibition and cardiovascular outcomes. Methods: We performed a systematic review and meta-analysis of the comparative effects of newer antiplatelet agents versus clopidogrel on major adverse cardiovascular events (MACE), all-cause mortality, myocardial infarction (MI), stroke, major bleeding and stent thrombosis, in patients with acute coronary syndromes (ACS) and/or undergoing percutaneous coronary intervention (PCI). Results: We identified 11 prospective randomized studies comparing newer antiplatelets to clopidogrel. The total number of participants included in meta-analysis was 70239. The total number of participants treated with clopidogrel was 34792 while 35447 patients were assigned to newer P2Y12 inhibitors, of which 29.4% received ticagrelor, 35.2% prasugrel and 35.4% were loaded with intravenous cangrelor. Ticagrelor use was associated with significantly reduced MACE, all-cause mortality, myocardial infarction and stent thrombosis and similar rates of stroke and major bleeding compared to clopidogrel in patients with ACS and/or PCI. Prasugrel use was associated with significantly lower rates of MACE, MI and stent thrombosis but significantly high rates of major bleeding and thus no all-cause mortality benefit compared to clopidogrel. Conclusion: Newer P2Y12 receptor antagonists are associated with better cardiovascular outcomes in patients with ACS and/or undergoing PCI. Prasugrel use resulted in higher major bleeding rates and no overall mortality benefit compared with clopidogrel.