title: Reduction in overall occurrences of ischemic events with vorapaxar: results from TRACER.
abstract: BACKGROUND
  Clinical trials traditionally use time-to-first-event analysis embedded within the composite endpoint of cardiovascular death (CVD), myocardial infarction (MI), or stroke. However, many patients have >1 event, and this approach may not reflect overall experience. We addressed this by analyzing all cardiovascular events in TRACER.
  
  
  RESULTS
  TRACER randomized 12 944 patients with non-ST-segment elevation acute coronary syndromes to placebo or to protease-activated receptor 1 antagonist vorapaxar with a median follow-up of 502 days (interquartile range, 349 to 667). Analysis of vorapaxar's effect on recurrent CVD, MI, or stroke was prespecified using the Wei, Lin, and Weissfeld approach. Vorapaxar did not reduce the first occurrence of the primary endpoint of CVD, MI, stroke, revascularization, or rehospitalization for recurrent ischemia, but reduced the secondary composite endpoint of CVD, MI, or stroke (14.7% vorapaxar vs. 16.4% placebo; hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.81 to 0.98; P=0.02; number needed to treat [NNT], 81). Recurrent secondary events occurred in 2.7% of patients. Vorapaxar reduced overall occurrences of ischemic events, first and subsequent (HR, 0.88; 95% CI, 0.80 to 0.98; P=0.02; NNT, 51). Also, there was a trend indicating that vorapaxar reduced the expanded endpoint, including revascularization and rehospitalization for recurrent ischemia (HR, 0.92; 95% CI, 0.84 to 1.01; P=0.09). Vorapaxar increased overall occurrences of moderate and severe Global Use of Strategies to Open Occluded Coronary Arteries bleeding (HR, 1.42; 95% CI, 1.21 to 1.66; P<0.001) and Thrombolysis in Myocardial Infarction clinically significant bleeding (HR, 1.550; 95% CI, 1.403 to 1.713; P<0.001).
  
  
  CONCLUSIONS
  Vorapaxar reduced overall occurrences of ischemic events, but increased bleeding. These exploratory findings broaden our understanding of vorapaxar's potential and expand our understanding of the value of capturing recurrent events.
  
  
  BACKGROUND
  ClinicalTrials.gov. Unique identifier: NCT00527943.
authors.affiliation: Green Lane Cardiovascular Service, Auckland City Hospital and Auckland University, Auckland, New Zealand (H.D.W.).
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.affiliation: Duke Clinical Research Institute, Durham, NC (Z.H., P.T., Y.L.).
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Duke Clinical Research Institute, Durham, NC (Z.H., P.T., Y.L.).
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Tricoci
authors.affiliation: Department of Cardiology, University of Leuven, Leuven, Belgium (F.V.W.).
authors.forename: Frans
authors.initials: F
authors.lastname: Van de Werf
authors.affiliation: Department of Medical Sciences, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden (L.W.).
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.affiliation: Duke Clinical Research Institute, Durham, NC (Z.H., P.T., Y.L.).
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Lokhnygina
authors.affiliation: Gill Heart Institute and Division of Cardiovascular Medicine, University of Kentucky, Lexington, KY (D.J.M.).
authors.forename: David J
authors.initials: DJ
authors.lastname: Moliterno
authors.affiliation: SAHMRI, Flinders University and Medical Center, Adelaide, Australia (P.E.A.).
authors.forename: Philip E
authors.initials: PE
authors.lastname: Aylward
authors.affiliation: Department of Medicine, Stanford University, Stanford, CA (K.W.M.).
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: Division of Cardiology, University of Alberta, Edmonton, Canada (P.W.A.).
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000368:Aged; D002318:Cardiovascular Diseases / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007511:Ischemia / Q000517:prevention & control*; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011725:Pyridines / Q000627:therapeutic use*; D012008:Recurrence; D055502:Secondary Prevention; D020521:Stroke / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; C530299:vorapaxar
keywords: acute coronary syndromes; recurrent events; vorapaxar