Comparison of Prasugrel and Bivalirudin vs Clopidogrel and Heparin in Patients With ST-Segment Elevation Myocardial Infarction: Design and Rationale of the Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 Trial

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for patients with ST-segment elevation myocardial infarction (STEMI). Effective and safe adjunct antithrombotic therapy is a major determinant for short- and long-term outcomes after primary PCI. Two separate studies have shown significant benefits vs conventional therapy for 2 recently approved drugs. In the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, bivalirudin after pretreatment with clopidogrel resulted in improved net clinical outcome compared with heparin plus glycoprotein IIb/IIIa inhibitors. However, during the first 24 hours after PCI, there was an increase in stent thrombosis rates with bivalirudin. In the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction (TRITON-TIMI) 38 trial, prasugrel was superior to clopidogrel in patients with acute coronary syndrome with and without ST-segment elevation. The synergic actions of prasugrel and bivalirudin may maximize the benefit of antithrombotic therapy for STEMI patients undergoing primary PCI. However, no specifically designed studies have so far compared the combination of prasugrel plus bivalirudin with that of clopidogrel plus unfractionated heparin in these patients. The Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 study is a randomized, open-label, multicenter trial aimed to test the hypothesis that a strategy based on prasugrel plus bivalirudin is superior to a strategy based on clopidogrel plus unfractionated heparin in terms of net clinical outcome in STEMI patients with planned primary PCI.