title: Usefulness and safety of vorapaxar in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention (from the TRACER Trial).
abstract: The therapeutic potential of vorapaxar in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention (PCI) is unknown. This prespecified analysis of a postrandomization subgroup evaluated the effects of vorapaxar compared with placebo among Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) participants undergoing PCI, focusing on the implanted stent type (drug-eluting stent [DES] vs bare-metal stent [BMS]). Among 12,944 recruited patients, 7,479 (57.8%) underwent PCI during index hospitalization, and 3,060 (40.9%) of those patients received exclusively BMS, whereas 4,015 (53.7%) received DES. The median (twenty-fifth, seventy-fifth percentiles) duration of thienopyridine therapy was 133 days (47, 246) with BMS and 221 days (88, 341) with DES. At 2 years among patients undergoing PCI, the primary (cardiovascular death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization) and secondary (cardiovascular death, myocardial infarction, or stroke) end points did not differ between vorapaxar and placebo groups, which was consistent with the treatment effect observed in the overall study population (p value for interaction = 0.540). However, the treatment effect trended greater (p value for interaction = 0.069) and the risk for bleeding in patients taking vorapaxar versus placebo appeared attenuated in BMS-only recipients. After adjustment for confounders, the interaction was no longer significant (p value = 0.301). The covariate that mostly explained the stent-type-by-treatment interaction was the duration of clopidogrel therapy. In conclusion, among patients with PCI, the effect of vorapaxar is consistent with the overall TRACER results. Patients who received a BMS underwent shorter courses of clopidogrel therapy and displayed trends toward greater ischemic benefit from vorapaxar and lesser bleeding risk, compared with patients who received a DES.
authors.affiliation: Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands. Electronic address: m.valgimigli@erasmusmc.nl.
authors.forename: Marco
authors.initials: M
authors.lastname: Valgimigli
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Tricoci
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Flinders University and Medical Centre, Bedford Park, Adelaide, Australia.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Aylward
authors.affiliation: Division of Cardiology, University of Alberta, Edmonton, Canada.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.affiliation: Department of Cardiology, University of Leuven, Leuven, Belgium.
authors.forename: Frans
authors.initials: F
authors.lastname: Van de Werf
authors.affiliation: Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Leonardi
authors.affiliation: Green Lane Cardiovascular Service, Auckland, New Zealand.
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.affiliation: University Hospital Kralovske Vinohrady, Charles University, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Widimsky
authors.affiliation: Department of Medicine, Stanford University, Stanford, California.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.affiliation: Hospital Universitari de Bellvitge, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Cequier
authors.affiliation: Bayer HealthCare Pharmaceuticals Inc., Whippany, New Jersey.
authors.forename: Edmond
authors.initials: E
authors.lastname: Chen
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Lokhnygina
authors.affiliation: Department of Medical Sciences, Uppsala Clinical Research Center, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.affiliation: Merck & Co., Whitehouse Station, New Jersey.
authors.forename: John
authors.initials: J
authors.lastname: Strony
authors.affiliation: Department of Medicine, Stanford University, Stanford, California.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, Kentucky.
authors.forename: David J
authors.initials: DJ
authors.lastname: Moliterno
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000503:physiopathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D054855:Drug-Eluting Stents; D004562:Electrocardiography; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007275:Injections, Intravenous; D007783:Lactones / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000379:methods*; D011183:Postoperative Complications / Q000453:epidemiology; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage*; D018179:Receptors, Thrombin / Q000037:antagonists & inhibitors; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D007783:Lactones; D011725:Pyridines; D018179:Receptors, Thrombin; C530299:vorapaxar