Positive Thrombotic and Thrombolytic Effects Observed with PAR-1 Antagonist Vorapaxar

SAN FRANCISCO, CA—Vorapaxar, a novel, oral PAR-1 antagonist that inhibits thrombin-induced platelet activation, was found to prolong occlusion time and shorten lysis time, with a favorable effect on thrombotic and thrombolytic status, results of a study presented at ACC.13, the American College of Cardiology's 62nd Annual Scientific Session, has found.

“In addition to its antiplatelet effect, vorapaxar significantly enhances thrombolytic status, which is frequently impaired in coronary disease,” noted Diana A. Gorog, MD, PhD, and colleagues from the Imperial College, London, UK. “This action could contribute to its atherothrombotic benefits and confer additional protection in those with impaired lysis time.”

The investigators performed a substudy in 57 patients from a single center enrolled in the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) and TRA2P-TIMI 50 studies to investigate the effect of vorapaxar on global thrombotic and thrombolytic status in patients with established atherosclerosis.

In TRACER, patients with non-ST-elevation acute coronary syndrome were randomized to vorapaxar given as a 40mg loading dose followed by 2.5mg/day or matching placebo within 24 hours of presentation. In TRA2P-TIMI 50, stable patients with a history of atherothrombosis, defined as a history of myocardial infarction, ischemic stroke, or peripheral arterial disease were randomized to either vorapaxar 2.5mg/day or matching placebo in addition to standard of care.

After more than 2 months of stabilization on treatment and again after treatment discontinuation, blood was tested with the point-of-care Global Thrombosis Test (GTT). The GTT uses non-anticoagulated blood to assess thrombotic and thrombolytic status by measuring the time required to form a shear-induced thrombus under physiological conditions (occlusion time) and, in the second phase of the test, measuring the time to achieve endogenous lysis of the thrombus (lysis time).

Dr. Gorog presented data demonstrating that vorapaxar treatment resulted in a longer occlusion time (median 561s [25th–75th percentile: 406–656] vs. 372s [322-459], P=0.002) and shorter lysis time (1158s [727–1529] vs. 1733s [1364–2268], P=0.015) than patients not receiving therapy. Patients receiving placebo showed no difference in occlusion or lysis time.

Compared to placebo, occlusion time was longer in patients taking vorapaxar than placebo (561s [406-656] vs. 419s [342-516], P=0.009), but lysis time was similar in both arms; vorapaxar 1158s (727-1529) vs. placebo 1236s (977-1613; P=0.28).