title: Vorapaxar in atherosclerotic disease management.
abstract: OBJECTIVE
  To review the pharmacology, efficacy, and safety of vorapaxar, a protease activator receptor-1 (PAR-1) antagonist, in the management of atherosclerotic diseases.
  
  
  METHODS
  Peer-reviewed clinical trials and review articles were identified from MEDLINE and Current Content database (both 1966 to December 31, 2014) using the search terms vorapaxar and protease activator receptor antagonist.
  
  
  METHODS
  A total of 30 clinical studies were identified (16 clinical trials, including subanalyses, 14 related to pharmacology, pharmacokinetics, and pharmacodynamics and drug interactions).
  
  
  RESULTS
  Two phase III clinical trials with vorapaxar have been published. In patients with non-ST segment elevation myocardial infarction (MI), vorapaxar failed to significantly reduce the primary efficacy end point (composite of cardiovascular death, MI, stroke, recurrent ischemia with hospitalization, and urgent coronary revascularization). Conversely, in a study of secondary prevention for patients with cardiovascular disease, the composite end point of cardiovascular death, MI, or stroke was significantly reduced. In both trials, the safety end points of major/minor bleeding were increased compared with placebo. In the secondary prevention trial, an increased incidence of intracranial hemorrhage led to the exclusion of patients with a prior history of stroke.
  
  
  CONCLUSIONS
  Vorapaxar is approved for use with aspirin and/or clopidogrel in the secondary prevention of cardiovascular events in stable patients with peripheral arterial disease or a history of MI. However, the addition of vorapaxar to other antiplatelets can significantly increase the risk of bleeding. It is, therefore, essential to balance the need for further reduction of risk of thrombotic event with patient's individual bleeding risk.
authors: MCPHS University, Boston, MA, USA Brigham and Women's Hospital, Boston, MA, USA judy.cheng@mcphs.edu.
authors: Judy W M
authors: JW
authors: Cheng
authors: The University of Montana, Missoula, MT, USA Providence/St Patrick Hospital and Health Sciences, Missoula, MT, USA.
authors: Vincent
authors: V
authors: Colucci
authors: University of Kansas Medical Center, Kansas City, KS, USA.
authors: Patricia A
authors: PA
authors: Howard
authors: South Carolina College of Pharmacy-MUSC Campus, Charleston, SC, USA Medical University of South Carolina, Charleston, SC, USA.
authors: Jean M
authors: JM
authors: Nappi
authors: University of the Sciences, Philadelphia, PA, USA.
authors: Sarah A
authors: SA
authors: Spinler
mesh_terms: D050197:Atherosclerosis / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D017326:Clinical Trials, Phase III as Topic; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007783:Lactones / Q000009:adverse effects / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000517:prevention & control; D058729:Peripheral Arterial Disease / Q000188:drug therapy; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D012306:Risk; D055502:Secondary Prevention; D020521:Stroke / Q000517:prevention & control; D016896:Treatment Outcome
chemical_list: D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; C530299:vorapaxar
keywords: atherosclerotic disease; protease activator receptor-1 antagonist; vorapaxar