Thrombin-receptor antagonist vorapaxar in acute coronary syndromes

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. CornelRafael 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

Research output: Contribution to journalArticlepeer-review

687 Citations (Scopus)


BACKGROUND: Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. METHODS: 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 a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. RESULTS: Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P = 0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P = 0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups. CONCLUSIONS: In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER number, NCT00527943.)

Original languageEnglish
Pages (from-to)20-33
Number of pages14
JournalNew England Journal of Medicine
Issue number1
Publication statusPublished - 5 Jan 2012
Externally publishedYes


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