title: Effect of vorapaxar on myocardial infarction in the thrombin receptor antagonist for clinical event reduction in acute coronary syndrome (TRA·CER) trial.
abstract: OBJECTIVE
  The TRA·CER trial compared vorapaxar, a novel platelet protease-activated receptor (PAR)-1 antagonist, with placebo in 12 944 patients with high-risk non-ST-segment elevation acute coronary syndromes (NSTE ACS). In this analysis, we explored the effect of vorapaxar on myocardial infarction (MI).
  
  
  RESULTS
  A blinded, independent central endpoint adjudication committee prospectively defined and classified MI according to the universal MI definition, including peak cardiac marker value (creatine kinase-MB [CK-MB] and/or troponin). Because the trial failed to meet its primary endpoint, these analyses are considered exploratory. During a median follow-up of 502 days, 1580 MIs occurred in 1319 patients. The majority (n = 1025, 64.9%) were type 1 (spontaneous) MI, followed by type 4a [percutaneous coronary intervention (PCI)-related] MI (n = 352; 22.3%). Compared with placebo, vorapaxar reduced the hazard of a first MI of any type by 12% [hazard ratio (HR), 0.88; 95% confidence interval (CI), 0.79-0.98; P = 0.021] and the hazard of total number of MIs (first and subsequent) by 14% (HR, 0.86; 95% CI, 0.77-0.97; P = 0.014), an effect that was sustained over time. Vorapaxar reduced type 1 MI by 17% (HR, 0.83; 95% CI, 0.73-0.95; P = 0.007). Type 4a MIs were not significantly reduced by vorapaxar (HR, 0.90; 95% CI, 0.73-1.12; P = 0.35). Vorapaxar effect was consistent across MI sizes defined by peak cardiac marker elevations and across key clinical subgroups; however, in patients not treated with thienopyridine at baseline (HR, 0.65; 95% CI, 0.46-0.92) compared with patients who received thienopyridine (HR, 0.91; 95% CI, 0.81-1.02), there was a trend towards a higher effect (Pint = 0.077).
  
  
  CONCLUSIONS
  The PAR-1 antagonist vorapaxar was associated with a reduction of MI, including total number of infarctions. This reduction was sustained over time and was mostly evident in type 1 MI, the most common type of MI observed.
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA. s.leonardi@smatteo.pv.it
authors.forename: Sergio
authors.initials: S
authors.lastname: Leonardi
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Tricoci
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.forename: Philip E
authors.initials: PE
authors.lastname: Aylward
authors.forename: David J
authors.initials: DJ
authors.lastname: Moliterno
authors.forename: Frans
authors.initials: F
authors.lastname: Van de Werf
authors.forename: Edmond
authors.initials: E
authors.lastname: Chen
authors.forename: Luis
authors.initials: L
authors.lastname: Providencia
authors.forename: Jan E
authors.initials: JE
authors.lastname: Nordrehaug
authors.forename: Claes
authors.initials: C
authors.lastname: Held
authors.forename: John
authors.initials: J
authors.lastname: Strony
authors.forename: Tyrus L
authors.initials: TL
authors.lastname: Rorick
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy*; D015415:Biomarkers / Q000378:metabolism; D052279:Creatine Kinase, MB Form / Q000378:metabolism; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D007783:Lactones / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000097:blood / Q000517:prevention & control*; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011446:Prospective Studies; D011725:Pyridines / Q000627:therapeutic use*; D014336:Troponin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D014336:Troponin; D052279:Creatine Kinase, MB Form; C530299:vorapaxar
keywords: Myocardial infarction; Thrombosis; Trials