title: Bivalirudin versus heparin with or without glycoprotein IIb/IIIa inhibitors in patients with STEMI undergoing primary percutaneous coronary intervention: pooled patient-level analysis from the HORIZONS-AMI and EUROMAX trials.
abstract: BACKGROUND
  In the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trial, 3,602 patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) treated with bivalirudin had lower bleeding and mortality rates, but higher acute stent thrombosis rates compared with heparin + a glycoprotein IIb/IIIa inhibitor (GPI). Subsequent changes in primary PCI, including the use of potent P2Y12 inhibitors, frequent radial intervention, and pre-hospital medication administration, were incorporated into the EUROMAX (European Ambulance Acute Coronary Syndrome Angiography) trial, which assigned 2,218 patients to bivalirudin versus heparin ± GPI before primary PCI.
  
  
  OBJECTIVE
  The goal of this study was to examine the outcomes of procedural anticoagulation with bivalirudin versus heparin ± GPI for primary PCI, given the evolution in primary PCI.
  
  
  METHODS
  Databases from HORIZONS-AMI and EUROMAX were pooled for patient-level analysis. The Breslow-Day test evaluated heterogeneity between trials.
  
  
  RESULTS
  A total of 5,800 patients were randomized to bivalirudin (n = 2,889) or heparin ± GPI (n = 2,911). The radial approach was used in 21.3% of patients, prasugrel/ticagrelor was used in 18.1% of patients, and GPI was used in 84.8% of the control group. Bivalirudin compared with heparin ± GPI resulted in reduced 30-day rates of major bleeding (4.2% vs. 7.8%; relative risk [RR]: 0.53; 95% confidence interval [CI]: 0.43 to 0.66; p < 0.0001), thrombocytopenia (1.4% vs. 2.9%, RR: 0.48; 95% CI: 0.33 to 0.71; p = 0.0002), and cardiac mortality (2.0% vs. 2.9%; RR: 0.70; 95% CI: 0.50 to 0.97; p = 0.03), with nonsignificantly different rates of reinfarction, ischemia-driven revascularization, stroke, and all-cause mortality. Bivalirudin resulted in increased acute (<24 h) stent thrombosis rates (1.2% vs. 0.2%; RR: 6.04; 95% CI: 2.55 to 14.31; p < 0.0001), with nonsignificantly different rates of subacute stent thrombosis. Composite net adverse clinical events were lower with bivalirudin (8.8% vs. 11.9%; RR: 0.74; 95% CI: 0.63 to 0.86; p < 0.0001). There was no significant heterogeneity between the 2 trials for these outcomes, and results were consistent across major subgroups.
  
  
  CONCLUSIONS
  Despite increased acute stent thrombosis, primary PCI with bivalirudin improved 30-day net clinical outcomes, with significant reductions in major bleeding, thrombocytopenia, and transfusions compared with heparin ± GPI, results that were consistent with evolution in PCI technique and pharmacotherapy. (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966) (European Ambulance Acute Coronary Syndrome Angiography [EUROMAX]; NCT01087723).
authors.affiliation: Columbia University Medical Center/New York-Presbyterian Hospital and 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: Mount Sinai Medical Center and the Cardiovascular Research Foundation, New York, New York.
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.affiliation: Lille University Hospital, Lille, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Goldstein
authors.affiliation: Helios Amperkliniken AG, Munich, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Witzenbichler
authors.affiliation: Isala Klinieken, Zwolle, the Netherlands.
authors.forename: Arnoud
authors.initials: A
authors.lastname: Van't Hof
authors.affiliation: Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Guagliumi
authors.affiliation: Kerckhoff Clinic and Thoraxcenter, Bad Nauheim, Germany.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Hamm
authors.affiliation: Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Quebec, Canada; Cardiovascular Research Foundation, New York, New York.
authors.forename: Philippe
authors.initials: P
authors.lastname: Généreux
authors.affiliation: Rigshospitalet, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Clemmensen
authors.affiliation: London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Pocock
authors.affiliation: Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Gersh
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: Efthymios N
authors.initials: EN
authors.lastname: Deliargyris
authors.affiliation: DHU FIRE, Université Paris-Diderot, Sorbonne Paris Cité, Paris, France; Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France; NHLI, Imperial College, Royal Brompton Hospital, London, United Kingdom.
authors.forename: Philippe Gabriel
authors.initials: PG
authors.lastname: Steg
mesh_terms: D000368:Aged; D000991:Antithrombins / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006493:Heparin / Q000627:therapeutic use*; D006629:Hirudins / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality / Q000628:therapy*; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D062645:Percutaneous Coronary Intervention; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000991:Antithrombins; D006629:Hirudins; D010446:Peptide Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D006493:Heparin; C074619:bivalirudin
keywords: angioplasty; anticoagulation; antiplatelet agents; myocardial infarction