title: Vorapaxar in patients with coronary artery bypass grafting: Findings from the TRA 2°P-TIMI 50 trial.
abstract: BACKGROUND
  Vorapaxar is a first-in-class protease-activated receptor-1 antagonist indicated for the reduction of cardiovascular death, myocardial infarction, and stroke in stable patients with prior atherothrombosis, who have not had a prior stroke or transient ischemic attack. The aims of this study were to investigate: 1) the role of vorapaxar in patients with severe coronary artery disease treated previously with coronary artery bypass grafting (CABG); and 2) safety in patients undergoing CABG while receiving vorapaxar.
  
  
  METHODS
  TRA 2°P-TIMI 50 was a randomized, double-blinded, placebo-controlled trial of vorapaxar in 26,449 stable patients with prior atherothrombosis followed for a median of 30 months. We 1) investigated the efficacy of vorapaxar among patients with a history of CABG prior to randomization ( n=2942); and 2) assessed the safety among 367 patients who underwent a new CABG during the trial.
  
  
  RESULTS
  Patients with a prior CABG were at higher risk for cardiovascular death, myocardial infarction, or stroke at three years compared with patients without a prior CABG (13.7% vs. 7.8%, p<0.001). Among patients with a prior CABG, vorapaxar significantly reduced the risk of cardiovascular death, myocardial infarction, or stroke (11.9% vs. 15.6%, hazard ratio 0.71, 95% confidence interval 0.58-0.88, p=0.001; number-needed-to-treat = 27). In patients undergoing CABG while receiving vorapaxar, the rate of Thrombolysis in Myocardial Infarction CABG major bleeding was 6.3% vs. 4.1% with placebo (hazard ratio 1.53, 95% confidence interval 0.58-4.01, p=0.39).
  
  
  CONCLUSIONS
  In patients with a prior CABG, vorapaxar significantly reduced the risk of recurrent major cardiovascular events. In patients undergoing CABG while receiving vorapaxar, bleeding risk appeared similar to that seen in the overall trial population.
authors.affiliation: 1 Department of Medicine, Brigham and Women's Hospital, Boston, USA.
authors.forename: Ethan C
authors.initials: EC
authors.lastname: Kosova
authors.affiliation: 2 TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, USA.
authors.forename: Marc P
authors.initials: MP
authors.lastname: Bonaca
authors.affiliation: 3 Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Dellborg
authors.affiliation: 2 TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: 4 Santo Andre's Hospital, Leiria, Portugal.
authors.forename: Joao
authors.initials: J
authors.lastname: Morais
authors.affiliation: 5 Canisius-Willhelmina Hospital, Nijmegen, The Netherlands.
authors.forename: Ton
authors.initials: T
authors.lastname: Oude Ophuis
authors.affiliation: 2 TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, USA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Scirica
authors.affiliation: 6 Third Division of Cardiology, Medical University of Silesia, Katowice, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Tendera
authors.affiliation: 7 Montreal Heart Institute, University of Montreal, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Theroux
authors.affiliation: 2 TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.affiliation: 2 TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Morrow
mesh_terms: D000368:Aged; D001026:Coronary Artery Bypass / Q000401:mortality*; D004311:Double-Blind Method; D005260:Female; D006331:Heart Diseases / Q000601:surgery*; D006801:Humans; D007783:Lactones / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage* / Q000627:therapeutic use; D055502:Secondary Prevention; D020521:Stroke / Q000517:prevention & control; D013927:Thrombosis / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; C530299:vorapaxar
keywords: CABG; Vorapaxar; antiplatelet; atherothrombosis; bleeding