title: Efficacy and safety of vorapaxar in patients with prior ischemic stroke.
abstract: OBJECTIVE
  Vorapaxar is an antiplatelet agent that antagonizes thrombin-mediated activation of the protease-activated receptor-1 on platelets. We tested the efficacy and safety of vorapaxar in a prespecified analysis in the stroke subcohort from a multinational, randomized, placebo-controlled trial.
  
  
  METHODS
  We randomly assigned patients with prior atherothrombosis (myocardial infarction, peripheral artery disease, or ischemic stroke) to receive vorapaxar (2.5 mg daily) or placebo added to standard antiplatelet therapy. Patients who qualified with stroke (N=4883) had a history of ischemic stroke in the prior 2 weeks to 12 months. The primary end point was the composite of cardiovascular death, myocardial infarction, or any stroke.
  
  
  RESULTS
  The qualifying stroke was classified as large vessel in 35%, small vessel in 47%, and other/unknown in 18%. In the stroke cohort, cardiovascular death, myocardial infarction, or stroke through 3 years was not reduced with vorapaxar versus placebo (13.0% vs 11.7%; hazard ratio, 1.03; 95% confidence interval, 0.85-1.25), including recurrent ischemic stroke (hazard ratio, 0.99; 95% confidence interval, 0.78-1.25). There were no significant differences in the effect of vorapaxar based on the type or timing of the qualifying stroke. Intracranial hemorrhage at 3 years was increased with vorapaxar (2.5% vs 1.0%; hazard ratio, 2.52; 95% confidence interval, 1.46-4.36).
  
  
  CONCLUSIONS
  In patients with prior ischemic stroke who receive standard antiplatelet therapy, adding vorapaxar increased the risk of intracranial hemorrhage without an improvement in major vascular events, including ischemic stroke. These findings add to the accumulating evidence establishing important risks with combination antiplatelet therapy in patients with prior stroke.  Clinical Trial Registration Information- http://www.clinicaltrials.gov. Unique identifier: NCT00526474.
authors: Brigham and Women's Hospital, Boston, MA 02115, USA. dmorrow@partners.org
authors: David A
authors: DA
authors: Morrow
authors: Mark J
authors: MJ
authors: Alberts
authors: Jay P
authors: JP
authors: Mohr
authors: Sebastian F
authors: SF
authors: Ameriso
authors: Marc P
authors: MP
authors: Bonaca
authors: Shinya
authors: S
authors: Goto
authors: Graeme J
authors: GJ
authors: Hankey
authors: Sabina A
authors: SA
authors: Murphy
authors: Benjamin M
authors: BM
authors: Scirica
authors: Eugene
authors: E
authors: Braunwald
mesh_terms: D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007391:International Cooperation; D020300:Intracranial Hemorrhages / Q000453:epidemiology*; D053208:Kaplan-Meier Estimate; D007783:Lactones / Q000009:adverse effects* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy; D058729:Peripheral Arterial Disease / Q000188:drug therapy; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects* / Q000627:therapeutic use*; D012307:Risk Factors; D020521:Stroke / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; C530299:vorapaxar