title: Universal Classification System Type of Incident Myocardial Infarction in Patients With Stable Atherosclerosis: Observations From Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P)-TIMI 50.
abstract: Our dual aims were as follows: (1) to classify new or recurrent myocardial infarctions (MI) in patients with stable atherosclerosis using the Universal Definition of MI classification system; and (2) to characterize the effects of vorapaxar, a first-in-class platelet protease-activated receptor -1 antagonist, on new or recurrent MI.
  
  
  
  We analyzed data from TRA 2°P-TIMI 50, a multinational, randomized, double-blind, placebo-controlled trial of vorapaxar. This analysis included 20 770 patients with previous MI or peripheral arterial disease without a history of transient ischemic attack or stroke. Each new or recurrent MI after randomization that met the trial end point definition was further categorized according to the European Society of Cardiology, American College of Cardiology, American Heart Association, World Heart Federation Universal Definition classification of type and size. Of 1095 incident MIs, 77% were spontaneous (Type 1), with a smaller number (9.8%) of secondary MIs (Type 2). Vorapaxar reduced Type 1 MI (hazard ratio [HR] 0.84, CI 0.73-0.98, P=0.024), with a similar pattern for Type 2 MI (HR 0.74, CI 0.49-1.10, P=0.13). Notably, vorapaxar showed a consistent pattern of reduction across size of MIs, including MIs in the highest Universal MI size class (≥10× upper reference limit, HR 0.83, CI 0.70-0.98, P=0.025). As such, there was a significant reduction in larger, spontaneous MIs (Type 1, ≥10× upper reference limit, HR 0.81, CI 0.67-0.99, P=0.036), and a consistent pattern with respect to fatal MI (HR 0.66, CI 0.39-1.11, P=0.12).
  
  
  
  Among stable patients with established atherosclerosis, the most common type of incident MI is spontaneous MI, and the reduction in MI with vorapaxar was consistent across MIs of varying type and size, including spontaneous infarctions ≥10× upper reference limit.
  
  
  
  URL: https://www.clinicaltrials.gov. Unique identifier: NCT00526474.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Kidd
authors.affiliation: TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Marc P
authors.initials: MP
authors.lastname: Bonaca
authors.affiliation: TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.affiliation: Department of Molecular Medicine, University of Pavia, Italy Department of Cardiology, Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy.
authors.forename: Gaetano M
authors.initials: GM
authors.lastname: De Ferrari
authors.affiliation: Lady Davis Carmel Medical Center and the Ruth and Bruce Rappaport School of Medicine, Technion, Haifa, Israel.
authors.forename: Basil S
authors.initials: BS
authors.lastname: Lewis
authors.affiliation: IV Divisione Cardiologia, Azienda Ospedaliera Niguarda Ca' Granda, Milan, Italy.
authors.forename: Piera A
authors.initials: PA
authors.lastname: Merlini
authors.affiliation: TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Murphy
authors.affiliation: TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Scirica
authors.affiliation: Green Lane Cardiovascular Service, Auckland City Hospital, West Auckland, New Zealand.
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.affiliation: TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA dmorrow@partners.org.
authors.forename: David A
authors.initials: DA
authors.lastname: Morrow
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000188:drug therapy*; D003324:Coronary Artery Disease / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000145:classification* / Q000453:epidemiology / Q000517:prevention & control; D058729:Peripheral Arterial Disease / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011725:Pyridines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D055502:Secondary Prevention
chemical_list: D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; C530299:vorapaxar
keywords: atherosclerosis; cardiovascular disease; myocardial infarction; platelet inhibitor