title: Reduction in cardiac mortality with bivalirudin in patients with and without major bleeding: The HORIZONS-AMI trial (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction).
abstract: OBJECTIVE
  The purpose of this study was to determine whether, in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), the reduction in cardiac mortality in those taking bivalirudin compared with unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor (UFH+GPI) can be fully attributed to reduced bleeding.
  
  
  BACKGROUND
  The association between hemorrhagic complications and mortality may explain the survival benefit with bivalirudin.
  
  
  METHODS
  A total of 3,602 STEMI patients undergoing primary PCI were randomized to bivalirudin versus UFH+GPI. Three-year cardiac mortality was analyzed in patients with and without major bleeding.
  
  
  RESULTS
  When compared with UFH+GPI, bivalirudin resulted in lower 3-year rates of major bleeding (6.9% vs. 10.5%, hazard ratio [HR]: 0.64 [95% confidence interval (CI): 0.51 to 0.80], p < 0.0001) and cardiac mortality (2.9% vs. 5.1%, HR: 0.56 [95% CI: 0.40 to 0.80], p = 0.001). Three-year cardiac mortality was reduced in bivalirudin-treated patients with major bleeding (20 fewer deaths with bivalirudin; 5.8% vs. 14.6%, p = 0.025) and without major bleeding (18 fewer deaths with bivalirudin; 2.6% vs. 3.8%, p = 0.048). In a fully-adjusted multivariable model accounting for major bleeding and other adverse events, bivalirudin was still associated with a 43% reduction in 3-year cardiac mortality (adjusted HR: 0.57 [95% CI: 0.39 to 0.83], p = 0.003).
  
  
  CONCLUSIONS
  Bivalirudin reduces cardiac mortality in patients with STEMI undergoing primary PCI, an effect that can only partly be attributed to prevention of bleeding. Further studies are required to identify the nonhematologic benefits of bivalirudin. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction; NCT00433966).
authors.affiliation: Columbia University Medical Center, New York, New York; The Cardiovascular Research Foundation, New York, New York. Electronic address: gs2184@columbia.edu.
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
authors.affiliation: London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Tim
authors.initials: T
authors.lastname: Clayton
authors.affiliation: The Medicines Company, Parsippany, New Jersey.
authors.forename: Efthymios N
authors.initials: EN
authors.lastname: Deliargyris
authors.affiliation: The Medicines Company, Parsippany, New Jersey.
authors.forename: Jayne
authors.initials: J
authors.lastname: Prats
authors.affiliation: The Cardiovascular Research Foundation, New York, New York; Mount Sinai Medical Center, New York, New York.
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.affiliation: London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Pocock
mesh_terms: D000368:Aged; D000991:Antithrombins / Q000008:administration & dosage; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000453:epidemiology / Q000517:prevention & control*; D006629:Hirudins / Q000008:administration & dosage*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D009204:Myocardial Revascularization / Q000379:methods*; D016017:Odds Ratio; D010446:Peptide Fragments / Q000008:administration & dosage*; D011379:Prognosis; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage; D015607:Stents; D015996:Survival Rate / Q000639:trends; D014481:United States / Q000453:epidemiology
chemical_list: D000991:Antithrombins; D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C074619:bivalirudin
keywords: CI; GPI; HR; PCI; ST-segment elevation myocardial infarction; STEMI; UFH; angioplasty; bivalirudin; complications; confidence interval; glycoprotein IIb/IIIa inhibitor; hazard ratio; myocardial infarction; percutaneous coronary intervention; prognosis; unfractionated heparin