title: Efficacy and Safety of Vorapaxar in Non-ST-Segment Elevation Acute Coronary Syndrome Patients Undergoing Noncardiac Surgery.
abstract: BACKGROUND
  Perioperative antiplatelet agents potentially increase bleeding after non-ST-segment elevation (NSTE) acute coronary syndromes (ACS). The protease-activated receptor 1 antagonist vorapaxar reduced cardiovascular events and was associated with increased bleeding versus placebo in NSTE ACS, but its efficacy and safety in noncardiac surgery (NCS) remain unknown. We aimed to evaluate ischemic, bleeding, and long-term outcomes of vorapaxar in NCS after NSTE ACS.
  
  
  RESULTS
  In the TRACER trial, 2202 (17.0%) patients underwent major or minor NCS after NSTE ACS over 1.5 years (median); continuing study treatment perioperatively was recommended. The primary ischemic end point for this analysis was cardiovascular death, myocardial infarction, stent thrombosis, or urgent revascularization within 30 days of NCS. Safety outcomes included 30-day NCS bleeding and GUSTO moderate/severe bleeding. Overall, 1171 vorapaxar and 1031 placebo patients underwent NCS. Preoperative aspirin and thienopyridine use was 96.8% versus 97.7% (P=0.235) and 89.1% versus 86.1% (P=0.036) for vorapaxar versus placebo, respectively. Within 30 days of NCS, no differences were observed in the primary ischemic end point between vorapaxar and placebo groups (3.4% versus 3.9%; adjusted odds ratio 0.81, 95% CI 0.50 to 1.33, P=0.41). Similarly, no differences in NCS bleeding (3.9% versus 3.4%; adjusted odds ratio 1.41, 95% CI 0.87 to 2.31, P=0.17) or GUSTO moderate/severe bleeding (4.2% versus 3.7%; adjusted odds ratio 1.15, 95% CI, 0.72 to 1.83, P=0.55) were observed. In a 30-day landmarked analysis, NCS patients had a higher long-term risk of the ischemic end point (adjusted hazard ratio 1.62, 95% CI 1.33 to 1.97, P<0.001) and GUSTO moderate/severe bleeding (adjusted hazard ratio 5.63, 95% CI 3.98 to 7.97, P<0.001) versus patients who did not undergo NCS, independent of study treatment.
  
  
  CONCLUSIONS
  NCS after NSTE ACS is common and associated with more ischemic outcomes and bleeding. Vorapaxar after NSTE ACS was not associated with increased perioperative ischemic or bleeding events in patients undergoing NCS.
authors.affiliation: Divisions of Critical Care and Cardiology, University of Alberta, Edmonton, Alberta, Canada (S.D.) Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada (S.D., M.P., C.M.W., P.W.A.).
authors.forename: Sean
authors.initials: S
authors.lastname: van Diepen
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (P.T.).
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Tricoci
authors.affiliation: Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada (S.D., M.P., C.M.W., P.W.A.).
authors.forename: Mohua
authors.initials: M
authors.lastname: Podder
authors.affiliation: Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada (S.D., M.P., C.M.W., P.W.A.).
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Westerhout
authors.affiliation: SAHMRI, Flinders University and Medical Centre, Adelaide, Australia (P.E.A.).
authors.forename: Philip E
authors.initials: PE
authors.lastname: Aylward
authors.affiliation: Department of Medical Sciences, Uppsala Clinical Research Center, Uppsala, Sweden (C.H., L.W.).
authors.forename: Claes
authors.initials: C
authors.lastname: Held
authors.affiliation: Department of Cardiology, University of Leuven, Belgium (F.V.W.).
authors.forename: Frans
authors.initials: F
authors.lastname: Van de Werf
authors.affiliation: Merck, Whitehouse Station, NJ (J.S.).
authors.forename: John
authors.initials: J
authors.lastname: Strony
authors.affiliation: Department of Medical Sciences, Uppsala Clinical Research Center, Uppsala, Sweden (C.H., L.W.).
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
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: Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand (H.D.W.).
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.affiliation: Stanford University, Stanford, CA (K.W.M., R.A.H.).
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: Stanford University, Stanford, CA (K.W.M., R.A.H.).
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.affiliation: Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada (S.D., M.P., C.M.W., P.W.A.) Division of Cardiology, University of Alberta, Edmonton, Alberta, Canada (P.W.A.).
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
mesh_terms: D054058:Acute Coronary Syndrome / Q000150:complications*; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006470:Hemorrhage / Q000517:prevention & control; D006801:Humans; D007783:Lactones / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D013514:Surgical Procedures, Operative / Q000379:methods*; D016896:Treatment Outcome; D010975:Platelet Aggregation Inhibitors
chemical_list: D007783:Lactones; D011725:Pyridines; C530299:vorapaxar; D010975:Platelet Aggregation Inhibitors
keywords: coronary disease; hemorrhage; noncardiac surgery; non–ST‐segment elevation acute coronary syndromes; surgery; vorapaxar