Thrombin-Receptor Antagonist Vorapaxar in Acute Coronary Syndromes

• DOI: 10.1056/nejmoa1109719
• Publication Date: 2011-11-13T13:01:11Z
• Authors: Pierluigi Tricoci; Zhen Huang; Claes Held; David J. Moliterno; Paul W. Armstrong; Frans Van de Werf; Harvey D. White; Philip E. Aylward; Lars Wallentin; Edmond Chen; Yuliya Lokhnygina; Jinglan Pei; Sergio Leonardi; Tyrus L. Rorick; Ann M. Kilian; Lisa H.K. Jennings; Giuseppe Ambrosio; Christoph Bode; Angel Cequier; Jan H. Cornel; Rafael Diaz; Aycan Erkan; Kurt Huber; Michael P. Hudson; Lixin Jiang; J. Wouter Jukema; Basil S. Lewis; A. Michael Lincoff; Gilles Montalescot; José Carlos Nicolau; Hisao Ogawa; Matthias Pfisterer; Juan Carlos Prieto; Witold Ruzyllo; Peter R. Sinnaeve; Robert F. Storey; Marco Valgimigli; David J. Whellan; Petr Widimsky; John Strony; Robert A. Harrington; Kenneth W. Mahaffey
• Keywords: Thrombin receptor

Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation.In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia rehospitalization, or urgent revascularization.Follow-up the trial terminated early after safety review. After median follow-up 502 days (interquartile range, 349 to 667), occurred 1031 6473 receiving versus 1102 6471 (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 1.01; P=0.07). A stroke 822 group 910 (14.7% and 16.4%, respectively; 0.89; CI, 0.81 0.98; P=0.02). Rates moderate severe bleeding were 7.2% 5.2% (hazard 1.35; 1.16 1.58; P<0.001). Intracranial hemorrhage rates 1.1% 0.2%, respectively 3.39; 1.78 6.45; nonhemorrhagic adverse events similar two groups.In syndromes, addition standard therapy did not significantly reduce but increased risk major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.).