Vorapaxar fails to improve outcomes

Thrombin is a key component in the coagulation cascade, cleaving fibrinogen to form insoluble fibrin, and also acting as a potent platelet activator through its action on protease activated receptors.  In the TRACER study the efficacy of the oral PAR-1 antagonist vorapaxar was assessed in patients presenting with non-ST elevation acute coronary syndromes.

In this industry sponsored, multinational, double-blind, randomized trial, vorapaxar was compared with placebo in 12,944 patients, in addition to standard dual antiplatelet therapy. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization.  The trial was terminated early following a safety review after a median follow-up of 502 days.  The primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (18.5% vs. 19.9%; HR, 0.92; 95% CI, 0.85 to 1.01; P=0.07).   However, vorapaxar significantly increased rates of moderate and severe bleeding from 5.2% in the placebo group to 7.2% (HR, 1.35; 95% CI, 1.16 to 1.58; P<0.001) including the important complication of intracranial hemorrhage with rates increasing 5-fold from 0.2% to 1.1% (HR, 3.39; 95% CI, 1.78 to 6.45; P<0.001).


In this large phase III study of patients with acute coronary syndromes, vorapaxar narrowly failed to show a significant benefit in its primary composite outcome of cardiovascular complications and death, but significantly increased the risk of major bleeding, including intracranial hemorrhage.

  • Tricoci P, Huang Z, Held C et al. Thrombin-Receptor Antagonist Vorapaxar in Acute Coronary Syndromes. N Engl J Med. 2011 Nov 13. [Epub ahead of print]

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