Abstract 19221: Rates of Arterial Revascularization in Patients Treated with Vorapaxar vs. Placebo in the TRA 2°P-TIMI 50 Trial

Abstract

Vorapaxar is a selective antagonist of protease-activated receptor (PAR)-1 that potently blocks platelet activation by thrombin. Thrombin signaling also influences vascular endothelial and smooth muscle function via PAR-1. Antagonism of PAR-1 reduces restenosis in animal models, suggesting the potential for vorapaxar to influence atherosclerotic disease progression. METHODS: The TRA2°P-TIMI 50 trial was a randomized, double-blind, placebo controlled trial of vorapaxar 2.5mg daily in 26,449 patients with stable atherosclerotic vascular disease, including prior myocardial infarction, stroke or peripheral arterial disease. Eligible patients had either an MI or ischemic stroke within the prior 2 weeks to 12 months or claudication with an ABI less than 0.85 or prior limb revascularization. We evaluated the rates of arterial revascularization in all patients included in the trial. RESULTS: Patients treated with vorapaxar had significantly lower rates of any arterial revascularization over 3 years as compared to placebo (13.6% versus 15.5%, HR 0.89; 95% CI 0.83-0.95, p<0.001). Specifically, the rates of revascularization were significantly lower with vorapaxar for both peripheral (3.9% versus 5.2%, p<0.001) and coronary vascular beds (9.7% versus 10.4%, p = 0.044), including a reduced rate of coronary artery bypass grafting (CABG) (1.7% versus 2.0%, p = 0.038). Moreover, elective revascularizations were reduced with vorapaxar (8.4% vs. 9.4%, p = 0.041). CONCLUSIONS: In this secondary analysis from a large randomized placebo-controlled trial, vorapaxar significantly reduced all arterial revascularizations suggesting possible clinical relevance of antagonism of PAR-1 mediated effects on endothelial or smooth muscle cells, as well as platelets.