Abstract 207: Vorapaxar in Patients with Prior Ischemic Stroke: Primary Results from the Stroke Cohort of the Multinational TRA 2°P-TIMI 50 Trial
Vorapaxar is an antiplatelet agent that potently inhibits thrombin-mediated activation of the platelet protease-activated receptor (PAR)-1. Phase 2 trials of vorapaxar suggested efficacy with acceptable safety in patients with ischemic stroke.
Methods: TRA 2°P–TIMI 50 was a multinational, randomized, double-blinded, placebo-controlled trial of 26449 patients with a history of atherothrombosis randomized to vorapaxar (2.5 mg daily) or matching placebo added to standard therapy, including antiplatelet agents. Patients who qualified with stroke (N=4883) had a history of ischemic stroke in the prior 2 wks to 12 mo. The first efficacy endpoint was the composite of cardiovascular (CV) death, MI, or stroke. After 2 years, the Data and Safety Monitoring Board recommended discontinuation of study treatment in patients with prior stroke.
Results: The qualifying stroke was classified as large vessel in 35%, small vessel in 47%, and other in 18%. Background therapy included aspirin in 81%, clopidogrel in 22%, and dipyridamole in 19%. In the stroke cohort, the 3-year rate of CV death, MI, or stroke was not reduced with vorapaxar vs. placebo (13.0% vs. 11.7%, HR 1.03; 95% CI 0.85-1.25), including recurrent ischemic stroke (HR 0.99; 95% CI 0.78-1.25). There were no statistically significant differences in the effect of vorapaxar based on the type or timing of the qualifying stroke, and a borderline interaction based on co-administration of clopidogrel (Figure) The rate of intracranial hemorrhage (ICH) at 3 years was 2.5% with vorapaxar vs. 1.0% with placebo (HR 2.52; 95% CI 1.46-4.36).
Conclusions: In patients with prior stroke receiving standard antiplatelet therapy, adding vorapaxar increased the risk of ICH without a reduction in the primary efficacy endpoint or ischemic stroke. These findings add to the accumulating evidence establishing important risks with combination antiplatelet therapy in patients with prior stroke.
- © 2012 by American Heart Association, Inc.