title: Efficacy and safety of vorapaxar as approved for clinical use in the United States.
abstract: BACKGROUND
  Vorapaxar is a protease-activated receptor-1 antagonist approved by the U.S. Food and Drug Administration (FDA) for the reduction of thrombotic cardiovascular (CV) events in patients with a history of myocardial infarction (MI) and peripheral artery disease (PAD), without a previous stroke or transient ischemic attack (TIA).
  
  
  RESULTS
  We examined the efficacy and safety of vorapaxar in the intended use population, considering 20,170 patients randomized in the multinational, double-blinded, placebo-controlled TRA 2°P-TIMI 50 trial. Of these, 16,897 qualified with a history of MI in the prior 2 weeks to 1 year and 3273 with PAD. At baseline 97% of the patients were treated with aspirin, 71% with a thienopyridine, and 93% a statin. At 3 years, the endpoint of CV death, MI, or stroke was significantly reduced with vorapaxar compared with placebo (7.9% versus 9.5%, HR, 0.80; 95% CI 0.73 to 0.89; P<0.001). Vorapaxar also significantly reduced the composite of CV death, MI, stroke, and urgent coronary revascularization (10.1% versus 11.8%, HR, 0.83; 95% CI 0.76 to 0.90; P<0.001), as well as the rate of CV death or MI (P<0.001). The safety endpoint of GUSTO moderate or severe bleeding, was increased in the vorapaxar group (3.7 versus 2.4, HR, 1.55; 95% CI 1.30 to 1.86, P<0.001). Intracranial bleeding (ICH) was 0.6% versus 0.4%, P=0.10 with vorapaxar versus placebo, with fatal bleeding 0.2% versus 0.2%; P=0.70.
  
  
  CONCLUSIONS
  In patients with prior MI or PAD who have not had a previous stroke or TIA, vorapaxar added to standard therapy is effective for long-term secondary prevention of thrombotic CV events, while increasing moderate or severe bleeding.
  
  
  BACKGROUND
  URL: clinicaltrials.gov Unique Identifier: NCT00526474.
authors: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (G.M., M.P.B., E.B., S.A.M., B.M.S., D.A.M.).
authors: Giulia
authors: G
authors: Magnani
authors: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (G.M., M.P.B., E.B., S.A.M., B.M.S., D.A.M.).
authors: Marc P
authors: MP
authors: Bonaca
authors: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (G.M., M.P.B., E.B., S.A.M., B.M.S., D.A.M.).
authors: Eugene
authors: E
authors: Braunwald
authors: Milpark Hospital, Johannesburg, South Africa (A.J.D.).
authors: Anthony J
authors: AJ
authors: Dalby
authors: Cardiovascular Research, University of Edinburgh, Edinburgh, UK (K.A.F.).
authors: Keith A A
authors: KA
authors: Fox
authors: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (G.M., M.P.B., E.B., S.A.M., B.M.S., D.A.M.).
authors: Sabina A
authors: SA
authors: Murphy
authors: Heart Institute (InCor)-University of São Paulo Medical School, São Paulo, Brazil (J.C.N.).
authors: José Carlos
authors: JC
authors: Nicolau
authors: Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands (T.O.O.).
authors: Ton
authors: T
authors: Oude Ophuis
authors: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (G.M., M.P.B., E.B., S.A.M., B.M.S., D.A.M.).
authors: Benjamin M
authors: BM
authors: Scirica
authors: University Hospital Brno, Masaryk University, Brno, Czech Republic (J.S.).
authors: Jindrich
authors: J
authors: Spinar
authors: Montreal Heart Institute and University of Montreal, Quebec, Canada (P.T.).
authors: Pierre
authors: P
authors: Theroux
authors: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (G.M., M.P.B., E.B., S.A.M., B.M.S., D.A.M.).
authors: David A
authors: DA
authors: Morrow
mesh_terms: D000368:Aged; D004311:Double-Blind Method; D017277:Drug Approval; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D002546:Ischemic Attack, Transient / Q000401:mortality / Q000517:prevention & control; D053208:Kaplan-Meier Estimate; D007783:Lactones / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D058729:Peripheral Arterial Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D044463:Receptor, PAR-1 / Q000378:metabolism; D012008:Recurrence; D012307:Risk Factors; D055502:Secondary Prevention / Q000379:methods*; D020521:Stroke / Q000401:mortality / Q000517:prevention & control; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration
chemical_list: D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D044463:Receptor, PAR-1; C530299:vorapaxar
keywords: antiplatelet therapy; atherosclerosis; myocardial infarction; peripheral arterial disease; secondary prevention; vorapaxar