title: Prasugrel plus bivalirudin vs. clopidogrel plus heparin in patients with ST-segment elevation myocardial infarction.
abstract: OBJECTIVE
  Whether prasugrel plus bivalirudin is a superior strategy to unfractionated heparin plus clopidogrel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) has never been assessed in specifically designed randomized trials.
  
  
  RESULTS
  The Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 study is an investigator-initiated, randomized, open-label, multicentre trial, designed to test the hypothesis that in STEMI patients with planned primary PCI a strategy based on prasugrel plus bivalirudin is superior to a strategy based on clopidogrel plus heparin in terms of net clinical outcome. Owing to slow recruitment, the trial was stopped prematurely after enrolment of 548 of 1240 planned patients. At 30 days, the primary composite endpoint of death, myocardial infarction, unplanned revascularization of the infarct related artery, stent thrombosis, stroke, or bleeding was observed in 42 patients (15.6%) randomized to prasugrel plus bivalirudin and 40 patients (14.5%) randomized to clopidogrel plus heparin [relative risk, 1.09; one-sided 97.5% confidence interval (CI) 0-1.79, P = 0.680]. The composite ischaemic endpoint of death, myocardial infarction, unplanned revascularization of the infarct-related artery, stent thrombosis, or stroke occurred in 13 patients (4.8%) in the prasugrel plus bivalirudin group and 15 patients (5.5%) in the clopidogrel plus heparin group (relative risk, 0.89; 95% CI 0.40-1.96, P = 0.894). Bleeding according to the HORIZONS-AMI definition was observed in 38 patients (14.1%) in the prasugrel plus bivalirudin group and 33 patients (12.0%) in the clopidogrel plus heparin group (relative risk, 1.18; 95% CI 0.74-1.88, P = 0.543). Results were consistent across various subgroups of patients.
  
  
  CONCLUSIONS
  In this randomized trial of STEMI patients, we were unable to demonstrate significant differences in net clinical outcome between prasugrel plus bivalirudin and clopidogrel plus heparin. Neither the composite of ischaemic complications nor bleeding were favourably affected by prasugrel plus bivalirudin compared with a regimen of clopidogrel plus unfractionated heparin. However, the results must be interpreted in view of the premature termination of the trial.
  
  
  BACKGROUND
  Unique identifier NCT00976092 (www.clinicaltrials.gov).
authors.affiliation: Deutsches Herzzentrum München, Technische Universität, Munich, Germany DZHK, Partner Site Munich Heart Alliance, Munich, Germany schulzs@dhm.mhn.de.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schulz
authors.affiliation: Herzzentrum Segeberger Kliniken GmbH, Bad Segeberg, Germany.
authors.forename: Gert
authors.initials: G
authors.lastname: Richardt
authors.affiliation: DZHK, Partner Site Munich Heart Alliance, Munich, Germany 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Karl-Ludwig
authors.initials: KL
authors.lastname: Laugwitz
authors.affiliation: Deutsches Herzzentrum München, Technische Universität, Munich, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Morath
authors.affiliation: Deutsches Herzzentrum München, Technische Universität, Munich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Neudecker
authors.affiliation: 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Hoppmann
authors.affiliation: Mount Sinai School of Medicine, New York, USA.
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester and NIHR Biomedical Research Unit in Cardiovascular Disease and University Hospitals of Leicester, Leicester, UK.
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Gershlick
authors.affiliation: Herzzentrum Segeberger Kliniken GmbH, Bad Segeberg, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Tölg
authors.affiliation: Deutsches Herzzentrum München, Technische Universität, Munich, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Anette Fiedler
authors.affiliation: Herzzentrum Segeberger Kliniken GmbH, Bad Segeberg, Germany.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdel-Wahab
authors.affiliation: Deutsches Herzzentrum München, Technische Universität, Munich, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kufner
authors.affiliation: 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Schneider
authors.affiliation: Deutsches Herzzentrum München, Technische Universität, Munich, Germany DZHK, Partner Site Munich Heart Alliance, Munich, Germany.
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
authors.affiliation: 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Tareq
authors.initials: T
authors.lastname: Ibrahim
authors.affiliation: DZHK, Partner Site Munich Heart Alliance, Munich, Germany Medizinische Klinik und Poliklinik I, Klinikum der LMU, Munich, Germany.
authors.forename: Julinda
authors.initials: J
authors.lastname: Mehilli
authors.affiliation: Deutsches Herzzentrum München, Technische Universität, Munich, Germany DZHK, Partner Site Munich Heart Alliance, Munich, Germany.
authors.forename: Adnan
authors.initials: A
authors.lastname: Kastrati
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D000077144:Clopidogrel; D017023:Coronary Angiography; D023921:Coronary Stenosis / Q000000981:diagnostic imaging; D004359:Drug Therapy, Combination; D057239:Early Termination of Clinical Trials; D006493:Heparin / Q000008:administration & dosage*; D006629:Hirudins / Q000008:administration & dosage*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy*; D010446:Peptide Fragments / Q000008:administration & dosage*; D010879:Piperazines / Q000008:administration & dosage*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D000068799:Prasugrel Hydrochloride; D011994:Recombinant Proteins / Q000008:administration & dosage; D013876:Thiophenes / Q000008:administration & dosage*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D006629:Hirudins; D010446:Peptide Fragments; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D013876:Thiophenes; D006493:Heparin; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine; C074619:bivalirudin
keywords: Bivalirudin; Clopidogrel; Heparin; Myocardial infarction; Prasugrel; Primary PCI