TRACER: Novel Antiplatelet Vorapaxar Runs Into Trouble in ACS

The novel antiplatelet vorapaxar, which blocks the thrombin receptor to inhibit platelet activation, ran into trouble in the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) trial, which was stopped prematurely earlier this year due to safety concerns.

TRACER was presented at the AHA by Ken Mahaffey and published simultaneously in the New England Journal of Medicine.

The trial randomized 12,944 patients with ACS, most of whom were receiving antiplatelet therapy. After enrollment in the trial was complete the followup was terminated early due to an increase in major bleeding, including intracerebral hemorrhage. (A companion trial, the TRA-2P TIMI 50 trial testing vorapaxar for secondary prevention, was not halted,  butt vorapaxar was discontinued in patients with a history of stroke.)

After a median follow-up of 502 days the primary endpoint, a composite of cardiovascular death, MI, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization, occurred in 18.5% of patients in the vorapaxar group versus 19.9% in the placebo group (HR 0.92, CI 0.85-1.01, p=0.07). The investigators reported a significant reduction in the composite endpoint of cardiovascular death, MI, or stroke, from 16.4% in the placebo group to 14.7% in the vorapaxar group (HR 0.89, CI 0.81-0.98, p=0.02).

However, moderate and severe bleeding occurred in 7.2% of the vorapaxar group and 5.2% of the placebo group (HR 1.35, CI 1.16-1.58, p<0.001). Intracranial hemorrhage occurred in 1.1% of the vorapaxar group versus 0.2% of the placebo group (HR 3.39, CI 1.78-6.45, p<0.001).

The investigators remained hopeful that future research might “lead to a better understanding of whether different strategies” of thrombin receptor blockade might be beneficial.

Trackbacks

  1. […] TRACER, the large ACS trial with vorapaxar, was terminated early last year due to similar safety concerns. As reported here last year, at the same time TRACER was stopped the TRA-2P trial was modified. TRA-2P investigator Eugene Braunwald said that vorapaxar would be discontinued in patients who experienced a stroke prior to entry or during the trial because of an increase in intracranial hemorrhage in these patients. […]

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