title: Thrombin-receptor antagonist vorapaxar in acute coronary syndromes.
abstract: BACKGROUND
  Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation.
  
  
  METHODS
  In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization.
  
  
  RESULTS
  Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups.
  
  
  CONCLUSIONS
  In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.).
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27705, USA. pierluigi.tricoci@duke.edu
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Tricoci
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
authors.forename: Claes
authors.initials: C
authors.lastname: Held
authors.forename: David J
authors.initials: DJ
authors.lastname: Moliterno
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.forename: Frans
authors.initials: F
authors.lastname: Van de Werf
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.forename: Philip E
authors.initials: PE
authors.lastname: Aylward
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.forename: Edmond
authors.initials: E
authors.lastname: Chen
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Lokhnygina
authors.forename: Jinglan
authors.initials: J
authors.lastname: Pei
authors.forename: Sergio
authors.initials: S
authors.lastname: Leonardi
authors.forename: Tyrus L
authors.initials: TL
authors.lastname: Rorick
authors.forename: Ann M
authors.initials: AM
authors.lastname: Kilian
authors.forename: Lisa H K
authors.initials: LH
authors.lastname: Jennings
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ambrosio
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.forename: Angel
authors.initials: A
authors.lastname: Cequier
authors.forename: Jan H
authors.initials: JH
authors.lastname: Cornel
authors.forename: Rafael
authors.initials: R
authors.lastname: Diaz
authors.forename: Aycan
authors.initials: A
authors.lastname: Erkan
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.forename: Michael P
authors.initials: MP
authors.lastname: Hudson
authors.forename: Lixin
authors.initials: L
authors.lastname: Jiang
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
authors.forename: Basil S
authors.initials: BS
authors.lastname: Lewis
authors.forename: A Michael
authors.initials: AM
authors.lastname: Lincoff
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Nicolau
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
authors.forename: Matthias
authors.initials: M
authors.lastname: Pfisterer
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Prieto
authors.forename: Witold
authors.initials: W
authors.lastname: Ruzyllo
authors.forename: Peter R
authors.initials: PR
authors.lastname: Sinnaeve
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
authors.forename: Marco
authors.initials: M
authors.lastname: Valgimigli
authors.forename: David J
authors.initials: DJ
authors.lastname: Whellan
authors.forename: Petr
authors.initials: P
authors.lastname: Widimsky
authors.forename: John
authors.initials: J
authors.lastname: Strony
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 / Q000188:drug therapy* / Q000628:therapy; D000368:Aged; D017130:Angioplasty; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control; D003131:Combined Modality Therapy; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D020300:Intracranial Hemorrhages / Q000139:chemically induced; D053208:Kaplan-Meier Estimate; D007783:Lactones / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; C530299:vorapaxar