title: Vorapaxar in patients with diabetes mellitus and previous myocardial infarction: findings from the thrombin receptor antagonist in secondary prevention of atherothrombotic ischemic events-TIMI 50 trial.
abstract: BACKGROUND
  Vorapaxar reduces cardiovascular death, myocardial infarction (MI), or stroke in patients with previous MI while increasing bleeding. Patients with diabetes mellitus (DM) are at high risk of recurrent thrombotic events despite standard therapy and may derive particular benefit from antithrombotic therapies. The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50 trial was a randomized, double-blind, placebo-controlled trial of vorapaxar in patients with stable atherosclerosis.
  
  
  RESULTS
  We examined the efficacy of vorapaxar in patients with and without DM who qualified for the trial with a previous MI. Because vorapaxar is contraindicated in patients with a history of stroke or transient ischemic attack, the analysis (n=16 896) excluded such patients. The primary end point of cardiovascular death, MI, or stroke occurred more frequently in patients with DM than in patients without DM (rates in placebo group: 14.3% versus 7.6%; adjusted hazard ratio, 1.47; P<0.001). In patients with DM (n=3623), vorapaxar significantly reduced the primary end point (11.4% versus 14.3%; hazard ratio, 0.73 [95% confidence interval, 0.60-0.89]; P=0.002) with a number needed to treat to avoid 1 major cardiovascular event of 29. The incidence of moderate/severe bleeding was increased with vorapaxar in patients with DM (4.4% versus 2.6%; hazard ratio, 1.60 [95% confidence interval, 1.07-2.40]). However, net clinical outcome integrating these 2 end points (efficacy and safety) was improved with vorapaxar (hazard ratio, 0.79 [95% confidence interval, 0.67-0.93]).
  
  
  CONCLUSIONS
  In patients with previous MI and DM, the addition of vorapaxar to standard therapy significantly reduced the risk of major vascular events with greater potential for absolute benefit in this group at high risk of recurrent ischemic events.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00526474.
authors: From TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.A.C., B.M.S., M.P.B., S.A.M., E.B., D.A.M.); University of Florida College of Medicine, Jacksonville (D.J.A.); Milpark Hospital, Johannesburg, South Africa (A.J.D.); Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital/Östra, Gothenburg, Sweden (M.D.); Santo Andre's Hospital, Leiria, Portugal (J.M.); Department of Cardiology, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands (T.O.O.); and Third Division of Cardiology, Medical University of Silesia, Katowice, Poland (M.T.).
authors: Matthew A
authors: MA
authors: Cavender
authors: From TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.A.C., B.M.S., M.P.B., S.A.M., E.B., D.A.M.); University of Florida College of Medicine, Jacksonville (D.J.A.); Milpark Hospital, Johannesburg, South Africa (A.J.D.); Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital/Östra, Gothenburg, Sweden (M.D.); Santo Andre's Hospital, Leiria, Portugal (J.M.); Department of Cardiology, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands (T.O.O.); and Third Division of Cardiology, Medical University of Silesia, Katowice, Poland (M.T.).
authors: Benjamin M
authors: BM
authors: Scirica
authors: From TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.A.C., B.M.S., M.P.B., S.A.M., E.B., D.A.M.); University of Florida College of Medicine, Jacksonville (D.J.A.); Milpark Hospital, Johannesburg, South Africa (A.J.D.); Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital/Östra, Gothenburg, Sweden (M.D.); Santo Andre's Hospital, Leiria, Portugal (J.M.); Department of Cardiology, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands (T.O.O.); and Third Division of Cardiology, Medical University of Silesia, Katowice, Poland (M.T.).
authors: Marc P
authors: MP
authors: Bonaca
authors: From TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.A.C., B.M.S., M.P.B., S.A.M., E.B., D.A.M.); University of Florida College of Medicine, Jacksonville (D.J.A.); Milpark Hospital, Johannesburg, South Africa (A.J.D.); Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital/Östra, Gothenburg, Sweden (M.D.); Santo Andre's Hospital, Leiria, Portugal (J.M.); Department of Cardiology, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands (T.O.O.); and Third Division of Cardiology, Medical University of Silesia, Katowice, Poland (M.T.).
authors: Dominick J
authors: DJ
authors: Angiolillo
authors: From TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.A.C., B.M.S., M.P.B., S.A.M., E.B., D.A.M.); University of Florida College of Medicine, Jacksonville (D.J.A.); Milpark Hospital, Johannesburg, South Africa (A.J.D.); Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital/Östra, Gothenburg, Sweden (M.D.); Santo Andre's Hospital, Leiria, Portugal (J.M.); Department of Cardiology, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands (T.O.O.); and Third Division of Cardiology, Medical University of Silesia, Katowice, Poland (M.T.).
authors: Anthony J
authors: AJ
authors: Dalby
authors: From TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.A.C., B.M.S., M.P.B., S.A.M., E.B., D.A.M.); University of Florida College of Medicine, Jacksonville (D.J.A.); Milpark Hospital, Johannesburg, South Africa (A.J.D.); Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital/Östra, Gothenburg, Sweden (M.D.); Santo Andre's Hospital, Leiria, Portugal (J.M.); Department of Cardiology, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands (T.O.O.); and Third Division of Cardiology, Medical University of Silesia, Katowice, Poland (M.T.).
authors: Mikael
authors: M
authors: Dellborg
authors: From TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.A.C., B.M.S., M.P.B., S.A.M., E.B., D.A.M.); University of Florida College of Medicine, Jacksonville (D.J.A.); Milpark Hospital, Johannesburg, South Africa (A.J.D.); Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital/Östra, Gothenburg, Sweden (M.D.); Santo Andre's Hospital, Leiria, Portugal (J.M.); Department of Cardiology, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands (T.O.O.); and Third Division of Cardiology, Medical University of Silesia, Katowice, Poland (M.T.).
authors: Joao
authors: J
authors: Morais
authors: From TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.A.C., B.M.S., M.P.B., S.A.M., E.B., D.A.M.); University of Florida College of Medicine, Jacksonville (D.J.A.); Milpark Hospital, Johannesburg, South Africa (A.J.D.); Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital/Östra, Gothenburg, Sweden (M.D.); Santo Andre's Hospital, Leiria, Portugal (J.M.); Department of Cardiology, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands (T.O.O.); and Third Division of Cardiology, Medical University of Silesia, Katowice, Poland (M.T.).
authors: Sabina A
authors: SA
authors: Murphy
authors: From TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.A.C., B.M.S., M.P.B., S.A.M., E.B., D.A.M.); University of Florida College of Medicine, Jacksonville (D.J.A.); Milpark Hospital, Johannesburg, South Africa (A.J.D.); Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital/Östra, Gothenburg, Sweden (M.D.); Santo Andre's Hospital, Leiria, Portugal (J.M.); Department of Cardiology, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands (T.O.O.); and Third Division of Cardiology, Medical University of Silesia, Katowice, Poland (M.T.).
authors: Ton Oude
authors: TO
authors: Ophuis
authors: From TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.A.C., B.M.S., M.P.B., S.A.M., E.B., D.A.M.); University of Florida College of Medicine, Jacksonville (D.J.A.); Milpark Hospital, Johannesburg, South Africa (A.J.D.); Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital/Östra, Gothenburg, Sweden (M.D.); Santo Andre's Hospital, Leiria, Portugal (J.M.); Department of Cardiology, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands (T.O.O.); and Third Division of Cardiology, Medical University of Silesia, Katowice, Poland (M.T.).
authors: Michal
authors: M
authors: Tendera
authors: From TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.A.C., B.M.S., M.P.B., S.A.M., E.B., D.A.M.); University of Florida College of Medicine, Jacksonville (D.J.A.); Milpark Hospital, Johannesburg, South Africa (A.J.D.); Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital/Östra, Gothenburg, Sweden (M.D.); Santo Andre's Hospital, Leiria, Portugal (J.M.); Department of Cardiology, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands (T.O.O.); and Third Division of Cardiology, Medical University of Silesia, Katowice, Poland (M.T.).
authors: Eugene
authors: E
authors: Braunwald
authors: From TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.A.C., B.M.S., M.P.B., S.A.M., E.B., D.A.M.); University of Florida College of Medicine, Jacksonville (D.J.A.); Milpark Hospital, Johannesburg, South Africa (A.J.D.); Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital/Östra, Gothenburg, Sweden (M.D.); Santo Andre's Hospital, Leiria, Portugal (J.M.); Department of Cardiology, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands (T.O.O.); and Third Division of Cardiology, Medical University of Silesia, Katowice, Poland (M.T.). dmorrow@partners.org.
authors: David A
authors: DA
authors: Morrow
mesh_terms: D000368:Aged; D003643:Death; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000453:epidemiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007783:Lactones / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000453:epidemiology; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D018179:Receptors, Thrombin / Q000037:antagonists & inhibitors*; D055502:Secondary Prevention / Q000379:methods / Q000639:trends*; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control*; D013927:Thrombosis / Q000453:epidemiology / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D007783:Lactones; D011725:Pyridines; D018179:Receptors, Thrombin; C530299:vorapaxar
keywords: coronary disease; diabetes mellitus; myocardial infarction; secondary prevention