Peripheral Revascularization in Patients With Peripheral Artery Disease With Vorapaxar: Insights From the TRA 2°P-TIMI 50 Trial

JACC Cardiovasc Interv. 2016 Oct 24;9(20):2157-2164. doi: 10.1016/j.jcin.2016.07.034.


Objectives: The aim of this study was to determine whether the reduction in peripheral revascularization with vorapaxar in patients with peripheral artery disease (PAD) is directionally consistent across indications, including acute limb ischemia, progressively disabling symptoms, or both.

Background: The protease-activated receptor-1 antagonist vorapaxar reduces peripheral revascularization in patients with PAD.

Methods: The TRA 2°P-TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction 50) trial randomized 26,449 patients with histories of myocardial infarction, stroke, or symptomatic PAD to vorapaxar or placebo on a background of standard therapy. A total of 5,845 patients had a known history of PAD at randomization. Peripheral revascularization procedures reported by the site were a pre-specified outcome. We explored whether the benefit of vorapaxar was consistent across indication and type of procedure.

Results: Of the 5,845 patients with known PAD, a total of 934 (16%) underwent at least 1 peripheral revascularization over 2.5 years (median). More than one-half (55%) were for worsening claudication, followed by critical limb ischemia (24%), acute limb ischemia (16%), and asymptomatic severe stenosis (4%). Vorapaxar significantly reduced peripheral revascularization (19.3% for placebo, 15.4% for vorapaxar; hazard ratio: 0.82; 95% confidence interval: 0.72 to 0.93; p = 0.003), with a consistent pattern of efficacy across indication.

Conclusions: Vorapaxar reduces peripheral revascularization in patients with PAD. This benefit of vorapaxar is directionally consistent across type of procedure and indication. (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: MALE; PAD; major adverse limb event(s); peripheral artery disease; peripheral intervention.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amputation
  • Endovascular Procedures* / adverse effects
  • Female
  • Humans
  • Lactones / adverse effects
  • Lactones / therapeutic use*
  • Limb Salvage
  • Male
  • Middle Aged
  • Peripheral Arterial Disease / diagnosis
  • Peripheral Arterial Disease / drug therapy*
  • Peripheral Arterial Disease / metabolism
  • Peripheral Arterial Disease / physiopathology
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Pyridines / adverse effects
  • Pyridines / therapeutic use*
  • Receptor, PAR-1 / antagonists & inhibitors*
  • Receptor, PAR-1 / metabolism
  • Time Factors
  • Treatment Outcome
  • Vascular Patency / drug effects
  • Vascular Surgical Procedures* / adverse effects


  • Lactones
  • Platelet Aggregation Inhibitors
  • Pyridines
  • Receptor, PAR-1
  • vorapaxar

Associated data