Coronary stent thrombosis with vorapaxar versus placebo: results from the TRA 2° P-TIMI 50 trial

J Am Coll Cardiol. 2014 Dec 9;64(22):2309-17. doi: 10.1016/j.jacc.2014.09.037. Epub 2014 Dec 1.


Background: Vorapaxar, a novel thrombin receptor antagonist, reduces cardiovascular death and recurrent thrombotic events when added to standard antiplatelet therapy in patients with stable atherosclerotic vascular disease.

Objectives: The goal of this study was to test the hypothesis that treatment with vorapaxar reduces the rate of coronary stent thrombosis (ST) in stable patients with a history of coronary stenting.

Methods: TRA 2° P-TIMI 50 (Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients With Atherosclerosis-Thrombolysis In Myocardial Infarction 50) was a multinational, randomized, double-blind, placebo-controlled trial of vorapaxar in stable patients with prior myocardial infarction, peripheral arterial disease, or stroke. We evaluated the rates of definite ST as adjudicated by a central events committee using Academic Research Consortium (ARC) criteria.

Results: A total of 26,449 patients were randomized, with 14,042 (53%) having a history of a coronary stent implantation before randomization, and an additional 449 patients receiving a coronary stent during the trial (total 14,491). During follow-up (median 2.5 years), there were 152 definite ST events, with the majority (92%) occurring late or very late. Vorapaxar reduced ARC definite ST (1.1% vs. 1.4%, hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.51 to 0.98; p = 0.037). The reduction was consistent, regardless of time from percutaneous coronary intervention, history of diabetes, use of drug-eluting stents, and use of dual antiplatelet therapy (DAPT) at randomization. Vorapaxar increased GUSTO moderate/severe bleeding (HR: 1.57, 95% CI: 1.26 to 1.94; p < 0.001).

Conclusions: The rate of ARC definite ST in stable patients, the majority of whom were receiving DAPT, was approximately 1.4% at 3 years. In stable patients with coronary stenting receiving standard antiplatelet therapy, vorapaxar administered for long-term secondary prevention significantly reduced ARC definite ST, including very late ST. (Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Patients With Atherosclerosis [TRA 2° P-TIMI 50] [P04737]; NCT00526474).

Keywords: DES; PAR-1; antiplatelet therapy; atherothrombosis; stent; thienopyridine.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Atherosclerosis / diagnosis
  • Atherosclerosis / drug therapy
  • Coronary Thrombosis / diagnosis*
  • Coronary Thrombosis / etiology
  • Coronary Thrombosis / prevention & control*
  • Double-Blind Method
  • Drug-Eluting Stents* / adverse effects
  • Female
  • Follow-Up Studies
  • Humans
  • Lactones / administration & dosage*
  • Male
  • Middle Aged
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / drug therapy
  • Pyridines / administration & dosage*
  • Receptors, Thrombin / antagonists & inhibitors*
  • Stroke / diagnosis
  • Stroke / drug therapy


  • Lactones
  • Pyridines
  • Receptors, Thrombin
  • vorapaxar

Associated data