Peropheral Arterial Disease

Vorapaxar in Patients with Peripheral Artery Disease: Results from TRA2°P-TIMI 50

1. Marc P. Bonaca1*; 
2. Benjamin M. Scirica1; 
3. Mark A. Creager1;
4. Jeffrey W. Olin2; 
5. Henri Bounameaux3; 
6. Mikael Dellborg4;
7. Jessica M. Lamp1; 
8. Sabina A. Murphy1; 
9. Eugene Braunwald1;
10. David A. Morrow1

+Author Affiliations

1. ¹Brigham and Women's Hospital and Harvard Medical School, Boston, MA
2. ²Mount Sinai School of Medicine, New York, NY
3. ³University Hospitals of Geneva, Geneva, Switzerland
4. ⁴Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital - Östra, Gothenburg, Sweden

1. ↵* Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115mbonaca@partners.org

Abstract

Background—Vorapaxar is a novel antagonist of protease-activated receptor (PAR)-1, the primary receptor for thrombin on human platelets that is also present on vascular endothelium and smooth muscle. Patients with peripheral artery disease (PAD) are at risk of systemic atherothrombotic events as well as acute and chronic limb ischemia and need for peripheral revascularization.

Methods and Results—The TRA2°P-TIMI 50 trial was a randomized, double-blind, placebo controlled trial of vorapaxar in 26,449 patients with stable atherosclerotic vascular disease (MI, stroke, or PAD). Patients with qualifying PAD (N= 3,787) had a history of claudication and ABI of <0 .85="" 0.39-0.86="" 0.58="" 0.73-0.97="" 0.78-1.14="" 0.84="" 0.94="" 1.21-2.18="" 1.62="" 11.9="" 22.2="" 3.9="" 4.5="" 95="" acute="" and="" artery="" bleeding.="" bleeding="" cardiovascular="" ci="" cohort="" compared="" death="" did="" differ="" efficacy="" endpoint="" for="" frequently="" gusto="" hospitalization="" however="" hr="" in="" ischemia.="" ischemia="" limb="" lower="" mi="" more="" not="" occurred="" of="" or="" p="0.001).</p" pad="" patients="" peripheral="" placebo="" primary="" principal="" prior="" randomized="" rates="" revascularization="" safety="" significantly="" stroke="" the="" to="" vorapaxar.="" vorapaxar="" vs.="" was="" were="" with="">

Conclusions—Vorapaxar did not reduce the risk of cardiovascular death, MI, or stroke in patients with PAD; however, vorapaxar significantly reduced acute limb ischemia and peripheral revascularization. The beneficial effects of PAR-1 antagonism on limb vascular events were accompanied by an increased risk of bleeding.

Clinical Trial Registration Information—http://www.clinicaltrials.gov;Identifier: NCT00526474.