title: One-Year Mortality for Bivalirudin vs Heparins Plus Optional Glycoprotein IIb/IIIa Inhibitor Treatment Started in the Ambulance for ST-Segment Elevation Myocardial Infarction: A Secondary Analysis of the EUROMAX Randomized Clinical Trial.
abstract: Uncertainty exists regarding potential survival benefits of bivalirudin compared with heparin with routine or optional use of glycoprotein IIb/IIIa inhibitors (GPIs) in patients with ST-segment elevation myocardial infarction (STEMI). Few data are available regarding long-term mortality in the context of contemporary practice with frequent use of radial access and novel platelet adenosine diphosphate P2Y12 receptor inhibitors.
  
  
  
  To assess the effect of bivalirudin monotherapy compared with unfractionated or low-molecular-weight heparin plus optional GPIs on 1-year mortality.
  
  
  
  This international, randomized, open-label clinical trial (EUROMAX [European Ambulance Acute Coronary Syndrome Angiography]) included 2198 patients with STEMI undergoing transport for primary percutaneous coronary intervention from March 10, 2010, through June 20, 2013, and followed up for 1 year. Patients were randomized (1:1) in ambulance to bivalirudin monotherapy vs unfractionated or low-molecular-weight heparin plus optional GPIs (control group). Analysis was based on intention to treat.
  
  
  
  The primary outcome of this prespecified analysis was 1-year mortality. All deaths were adjudicated as cardiac or noncardiac by an independent, blinded clinical events committee. One-year mortality was assessed and examined across multiple prespecified subgroups.
  
  
  
  Of the 2198 patients enrolled (1675 men [76.2%] and 523 women [23.8%]; median [interquartile range] age, 62 [52-72] years), complete 1-year follow-up data were available for 2164 (98.5%). All-cause 1-year mortality occurred in 118 patients (5.4%). The number of all-cause deaths was the same for both treatment groups (59 deaths; relative risk [RR], 1.02; 95% CI, 0.72-1.45; P = .92). No differences were noted in the rates of 1-year cardiac death (44 [4.0%] for the bivalirudin group vs 48 [4.3%] for the control group; RR, 0.93; 95% CI, 0.63-1.39; P = .74) or noncardiac death (15 [1.4%] for the bivalirudin group vs 11 [1.0%] for the control group; RR, 1.39; 95% CI, 0.64-3.01; P = .40). Results were consistent across the prespecified patient subgroups. The rate of deaths occurring from 30 days to 1 year was also similar (27 [2.5%] in the bivalirudin group vs 25 [2.3%] in the control group; RR, 1.10; 95% CI, 0.64-1.88; P = .73).
  
  
  
  In patients with STEMI who were being transported for primary percutaneous coronary intervention, treatment with bivalirudin or with heparin with optional use of GPI resulted in similar 1-year mortality. The reduced composite end point of death and/or major bleeding at 30 days in the bivalirudin arm of the EUROMAX trial did not translate into reduced cardiovascular or all-cause death at 1 year.
  
  
  
  clinicaltrials.gov Identifier: NCT01087723.
authors.affiliation: Department of Cardiology, Isala Hospital, Zwolle, the Netherlands2Cardiovascular Department, Azienda Sanitaria Universitaria Integrata, University of Trieste, Trieste, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Fabris
authors.affiliation: Department of Cardiology, Isala Hospital, Zwolle, the Netherlands.
authors.forename: Sinem
authors.initials: S
authors.lastname: Kilic
authors.affiliation: Department of Cardiology, Isala Hospital, Zwolle, the Netherlands.
authors.forename: Arnoud W J
authors.initials: AWJ
authors.lastname: Van't Hof
authors.affiliation: Department of Cardiology, St Antonius Hospital, Nieuwegein, the Netherlands.
authors.forename: Jurrien
authors.initials: J
authors.lastname: Ten Berg
authors.affiliation: Department of Cardiology, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ayesta
authors.affiliation: Department of Cardiology, Klinikum Ludwigshafen, Ludwigshafen, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Zeymer
authors.affiliation: Department of Clinical Research, University of Caen, Caen, France.
authors.forename: Martial
authors.initials: M
authors.lastname: Hamon
authors.affiliation: Services d'Aide Médicale Urgente, Service Mobile d'Urgence et de Réanimation Urgences, Centre Hospitalier, Chateauroux, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Soulat
authors.affiliation: The Medicines Company, Parsippany, New Jersey.
authors.forename: Debra
authors.initials: D
authors.lastname: Bernstein
authors.affiliation: The Medicines Company, Parsippany, New Jersey.
authors.forename: Prodromos
authors.initials: P
authors.lastname: Anthopoulos
authors.affiliation: The Medicines Company, Parsippany, New Jersey.
authors.forename: Efthymios N
authors.initials: EN
authors.lastname: Deliargyris
authors.affiliation: Institut National de la Santé et de la Recherche Medicale U-1148, Département Hospitalo-Universitaire FIRE (Fibrosis Inflammation Remodeling), Université Paris-Diderot, Paris, France 10Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France11National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London, England.
authors.forename: Philippe Gabriel
authors.initials: PG
authors.lastname: Steg
mesh_terms: D000368:Aged; D000552:Ambulances; D000925:Anticoagulants / Q000627:therapeutic use; D000991:Antithrombins / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004632:Emergency Medical Services; D005260:Female; D006493:Heparin / Q000627:therapeutic use*; D006629:Hirudins; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality; D010446:Peptide Fragments / Q000627:therapeutic use*; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000627:therapeutic use; D000072657:ST Elevation Myocardial Infarction / Q000628:therapy*
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D006629:Hirudins; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D006493:Heparin; C074619:bivalirudin