title: Vorapaxar, a platelet thrombin-receptor antagonist, in medically managed patients with non-ST-segment elevation acute coronary syndrome: results from the TRACER trial.
abstract: BACKGROUND
  This study characterized a medically managed population in a non-ST-segment elevation acute coronary syndrome (NSTEACS) cohort and evaluated prognosis and outcomes of vorapaxar vs. placebo.
  
  
  METHODS
  In the TRACER study, 12,944 NSTEACS patients were treated with standard care and vorapaxar (a novel platelet protease-activated receptor-1 antagonist) or placebo. Of those, 4194 patients (32.4%) did not undergo revascularization during index hospitalization, and 8750 (67.6%) underwent percutaneous coronary intervention or coronary artery bypass grafting. Patients managed medically were heterogeneous with different risk profiles, including 1137 (27.1%) who did not undergo coronary angiography. Patients who underwent angiography but were selected for medical management included those without evidence of significant coronary artery disease (CAD), with prior CAD but no new significant lesions, and with significant lesions who were not treated with revascularization.
  
  
  RESULTS
  Cardiovascular event rates were highest among those without angiography and lowest in the group with angiography but without CAD. In the medically managed cohort, 2-year primary outcome (cardiovascular death, myocardial infarction, stroke, recurrent ischaemia with rehospitalization, urgent coronary revascularization) event rates were 16.3% with vorapaxar and 17.0% with placebo (HR 0.99, 95% CI 0.83-1.17), with no interaction between drug and management strategy (p=0.75). Key secondary endpoint (cardiovascular death, myocardial infarction, stroke) rates were 13.4% with vorapaxar and 14.9% with placebo (HR 0.89, 95% CI 0.74-1.07), with no interaction (p=0.58). Vorapaxar increased GUSTO moderate/severe bleeding numerically in medically managed patients (adjusted HR 1.46, 95% CI 0.99-2.15).
  
  
  CONCLUSIONS
  NSTEACS patients who were initially medically managed had a higher risk-factor burden, and one-third had normal coronary arteries. Outcome in the medically managed cohort was significantly related to degree of CAD, highlighting the importance of coronary angiography. Efficacy and safety of vorapaxar appeared consistent with the overall trial results.
authors.affiliation: Department of Medical Sciences, Cardiology, Uppsala University/Uppsala Clinical Research Center, Uppsala, Sweden claes.held@ucr.uu.se.
authors.forename: Claes
authors.initials: C
authors.lastname: Held
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Tricoci
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
authors.affiliation: University of Leuven, Leuven, Belgium.
authors.forename: Frans
authors.initials: F
authors.lastname: Van de Werf
authors.affiliation: Auckland City Hospital, Auckland, New Zealand.
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.affiliation: University of Alberta, Edmonton, Canada.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.affiliation: University of Perugia, Perugia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ambrosio
authors.affiliation: Flinders University and Medical Centre, Adelaide, Australia.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Aylward
authors.affiliation: University of Kentucky, Lexington, KY, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Moliterno
authors.affiliation: Department of Medical Sciences, Cardiology, Uppsala University/Uppsala Clinical Research Center, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.affiliation: Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA.
authors.forename: Edmond
authors.initials: E
authors.lastname: Chen
authors.affiliation: Ufuk University, Ankara, Turkey.
authors.forename: Aycan
authors.initials: A
authors.lastname: Erkan
authors.affiliation: Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Merck, Whitehouse Station, NJ, USA.
authors.forename: John
authors.initials: J
authors.lastname: Strony
authors.affiliation: Stanford University, Stanford, CA, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.affiliation: Stanford University, Stanford, CA, USA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D012008:Recurrence; D012307:Risk Factors; D020521:Stroke / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; C530299:vorapaxar
keywords: Myocardial infarction; platelet receptor blockers; thrombosis