title: Effect of age on efficacy and safety of vorapaxar in patients with non-ST-segment elevation acute coronary syndrome: Insights from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial.
abstract: Antithrombotic therapy plays an important role in the treatment of non-ST-segment elevation acute coronary syndromes (NSTE ACS) but is associated with bleeding risk. Advanced age may modify the relationship between efficacy and safety.
  
  
  
  Efficacy and safety of vorapaxar (a protease-activated receptor 1 antagonist) was analyzed across ages as a continuous and a categorical variable in the 12,944 patients with NSTE ACS enrolled in the TRACER trial. To evaluate the effect of age, Cox regression models were developed to estimate hazard ratios (HRs) with the adjustment of other baseline characteristics and randomized treatment for the primary efficacy composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization, and the primary safety composite of moderate or severe Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding.
  
  
  
  The median age of the population was 64years (25th, 75th percentiles = 58, 71). Also, 1,791 patients (13.8%) were ≤54years of age, 4,968 (38.4%) were between 55 and 64 years, 3,979 (30.7%) were between 65 and 74 years, and 2,206 (17.1%) were 75years or older. Older patients had higher rates of hypertension, renal insufficiency, and previous stroke and worse Killip class. The oldest age group (≥75years) had substantially higher 2-year rates of the composite ischemic end point and moderate or severe GUSTO bleeding compared with the youngest age group (≤54years). The relationships between treatment assignment (vorapaxar vs placebo) and efficacy outcomes did not vary by age. For the primary efficacy end point, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were as follows: 1.12 (0.88-1.43), 0.88 (0.76-1.02), 0.89 (0.76-1.04), and 0.88 (0.74-1.06), respectively (P value for interaction = .435). Similar to what was observed for efficacy outcomes, we did not observe any interaction between vorapaxar and age on bleeding outcomes. For the composite of moderate or severe bleeding according to the GUSTO classification, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were 1.73 (0.89-3.34), 1.39 (1.04-1.86), 1.10 (0.85-1.42), and 1.73 (1.29-2.33), respectively (P value for interaction = .574).
  
  
  
  Older patients had a greater risk for ischemic and bleeding events; however, the efficacy and safety of vorapaxar in NSTE ACS were not significantly influenced by age.
authors: Brazilian Clinical Research Institute, São Paulo, Brazil.
authors: Luciana V
authors: LV
authors: Armaganijan
authors: Duke Clinical Research Institute, Durham, NC.
authors: Karen P
authors: KP
authors: Alexander
authors: Duke Clinical Research Institute, Durham, NC.
authors: Zhen
authors: Z
authors: Huang
authors: Duke Clinical Research Institute, Durham, NC.
authors: Pierluigi
authors: P
authors: Tricoci
authors: Department of Medical Sciences, Cardiology, and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors: Claes
authors: C
authors: Held
authors: Department of Cardiology, University Hospitals Leuven, Leuven, Belgium.
authors: Frans
authors: F
authors: Van de Werf
authors: University of Alberta, Edmonton, AB, Canada.
authors: Paul W
authors: PW
authors: Armstrong
authors: South Australian Health and Medical Research Institute, Flinders University and Medical Center, Adelaide, Australia.
authors: Philip E
authors: PE
authors: Aylward
authors: Green Lane Cardiovascular Service, Auckland, New Zealand.
authors: Harvey D
authors: HD
authors: White
authors: Gill Heart Institute and University of Kentucky, Lexington, KY.
authors: David J
authors: DJ
authors: Moliterno
authors: Department of Medical Sciences, Cardiology, and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors: Lars
authors: L
authors: Wallentin
authors: Bayer HealthCare Pharmaceuticals Inc, Whippany, NJ.
authors: Edmond
authors: E
authors: Chen
authors: Department of Medicine, Stanford University, Stanford, CA.
authors: Robert A
authors: RA
authors: Harrington
authors: Johnson & Johnson, New Brunswick, NJ.
authors: John
authors: J
authors: Strony
authors: Department of Medicine, Stanford University, Stanford, CA.
authors: Kenneth W
authors: KW
authors: Mahaffey
authors: Duke Clinical Research Institute, Durham, NC. Electronic address: renato.lopes@duke.edu.
authors: Renato D
authors: RD
authors: Lopes
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000367:Age Factors; D000368:Aged; D002318:Cardiovascular Diseases / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D009204:Myocardial Revascularization; D010359:Patient Readmission; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011725:Pyridines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D020521:Stroke / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; C530299:vorapaxar