Optimal P2Y12 Inhibitor for Primary PCI STEMI Patients

Study Questions:

What is the comparative clinical efficacy and safety of P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous intervention (PPCI)?


Clinical trials enrolling STEMI patients were identified and relevant data were extracted. Major adverse cardiovascular events (MACE) were defined as the composite of all-cause mortality, MI, and target vessel revascularization. Network meta-analysis was performed using Bayesian methods.


A total of 37 studies with 88,402 STEMI patients and 5,077 MACE were analyzed. Outcomes at 1 month (22 studies and 60,783 patients) suggest that prasugrel was associated with: lower MACE than clopidogrel (standard dose odds ratio [OR], 0.59; 95% confidence interval [CI], 0.50-0.69; high dose OR, 0.60; 95% CI, 0.51-0.71; upstream OR, 0.79; 95% CI, 0.66-0.94), and ticagrelor (standard dose OR, 0.69; 95% CI, 0.56-0.84; upstream OR, 0.72; 95% CI, 0.50-1.05); lower mortality and MI than clopidogrel and standard ticagrelor; lower stroke risk than standard clopidogrel and standard or upstream ticagrelor; and lower stent thrombosis than standard or upstream clopidogrel. At 1 year (10 studies, 40,333 patients), prasugrel was associated with lower mortality and MACE than other P2Y12 inhibitors. MACE was particularly lower with prasugrel in studies where patients received bivalirudin, drug-eluting stents, but not glycoprotein IIb/IIIa inhibitor.


The authors concluded that in STEMI patients undergoing PPCI, prasugrel and ticagrelor were more efficacious than clopidogrel. In addition, prasugrel was superior to ticagrelor, particularly in conjunction with bivalirudin and drug-eluting stents.


This network meta-analysis reports that in STEMI patients undergoing PPCI, prasugrel and ticagrelor are associated with better clinical outcomes than standard- or high-dose clopidogrel at 1 year; and prasugrel appears superior to standard ticagrelor at both 1 month and 1 year. Prasugrel appears to be particularly more effective in patients receiving bivalirudin and drug-eluting stents. These data underscore the need for a randomized clinical trial to compare the efficacy and safety of various P2Y12 inhibitors in STEMI patients and provide definitive evidence on the superiority of one agent over another. As we accrue new evidence, the intensity, type, and duration of P2Y12 inhibitor therapy will need to be tailored to each patient’s need, balancing ischemic and bleeding risks.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Anticoagulation Management and ACS, Aortic Surgery, Interventions and ACS

Keywords: Acute Coronary Syndrome, Adenosine, Drug-Eluting Stents, Glycoproteins, Hirudins, Myocardial Infarction, Myocardial Revascularization, Peptide Fragments, Percutaneous Coronary Intervention, Stroke, Thrombosis, Ticlopidine, Treatment Outcome

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