title: Impact of time to treatment on the effects of bivalirudin vs. glycoprotein IIb/IIIa inhibitors and heparin in patients undergoing primary percutaneous coronary intervention: insights from the HORIZONS-AMI trial.
abstract: OBJECTIVE
  In the HORIZONS-AMI trial, bivalirudin compared to unfractionated heparin (UFH) plus a glycoprotein IIb/IIIa inhibitor (GPI) improved net clinical outcomes in patients undergoing primary percutaneous coronary intervention (PCI) at the cost of an increased rate of acute stent thrombosis. We sought to examine whether these effects are dependent on time to treatment.
  
  
  RESULTS
  The interaction between anticoagulation regimen and symptom onset to first balloon inflation time (SBT) on the 30-day and three-year rates of major adverse cardiac events (MACE) was examined in 3,199 randomised patients according to SBT ≤3 hours versus >3 hours. Among patients with an SBT ≤3 hours, bivalirudin resulted in higher 30-day rates of MACE compared to UFH plus a GPI. Non-significant differences were observed in patients with an SBT >3 hours. Similar results were found for MACE at three years and stent thrombosis and reinfarction at 30 days and three years. By multivariable analysis, bivalirudin was an independent predictor of MACE at 30 days and three years in patients with an SBT ≤3 hours, but not in patients with SBT >3 hours.
  
  
  CONCLUSIONS
  Bivalirudin compared to UFH plus a GPI is associated with an increased rate of stent thrombosis and MACE in patients with short SBTs, but not in those with longer SBTs.
authors.affiliation: Mount Sinai Medical Center, New York, NY, USA.
authors.forename: Mikkel M
authors.initials: MM
authors.lastname: Schoos
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Luca
authors.forename: George D
authors.initials: GD
authors.lastname: Dangas
authors.forename: Peter
authors.initials: P
authors.lastname: Clemmensen
authors.forename: Girma Minalu
authors.initials: GM
authors.lastname: Ayele
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D000991:Antithrombins / Q000627:therapeutic use*; D002423:Cause of Death; D004359:Drug Therapy, Combination; D005260:Female; D006083:Graft Occlusion, Vascular / Q000453:epidemiology; D006493:Heparin / Q000627:therapeutic use*; D006629:Hirudins; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009203:Myocardial Infarction / Q000453:epidemiology; D009204:Myocardial Revascularization / Q000706:statistics & numerical data; D010446:Peptide Fragments / Q000627:therapeutic use*; D062645:Percutaneous Coronary Intervention / Q000379:methods*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011183:Postoperative Complications / Q000453:epidemiology; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D000072657:ST Elevation Myocardial Infarction / Q000628:therapy*; D020521:Stroke / Q000453:epidemiology; D013927:Thrombosis / Q000453:epidemiology; D061665:Time-to-Treatment / Q000706:statistics & numerical data*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D006629:Hirudins; D010446:Peptide Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D006493:Heparin; C074619:bivalirudin