The Efficacy and Safety of Vorapaxar With and Without a Thienopyridine for Secondary Prevention in Patients with Prior Myocardial Infarction and no History of Stroke or TIA: Results from TRA 2°P-TIMI 50
Background—Vorapaxar antagonizes protease-activated receptor (PAR)-1, the primary receptor for thrombin on human platelets, and reduces recurrent thrombotic events in stable patients with a prior myocardial infarction (MI). We wished to determine whether the efficacy and safety of antiplatelet therapy with vorapaxar was modified by concurrent thienopyridine use.
Methods and Results—TRA 2°P-TIMI 50 was a randomized, double-blind, placebo-controlled trial of vorapaxar in 26,449 patients with prior atherothrombosis. This pre-specified analysis included 16,897 patients who qualified with a MI in the preceding 2 weeks to 12 months and was restricted to patients without a history of stroke or TIA given its contraindication in that population. Randomization was stratified on the basis of planned thienopyridine use. Thienopyridine was planned at randomization in 12,410 (73%). Vorapaxar significantly reduced the composite of cardiovascular death, MI and stroke when compared to placebo regardless of planned thienopyridine therapy (planned thienopyridine HR 0.80, 0.70-0.91, p<0.001; no planned thienopyridine HR 0.75, 0.60-0.94, p=0.011; p-interaction=0.67). Findings were similar when patients were stratified by actual thienopyridine use at baseline (p-interaction=0.82) and through 18 months (p-interaction=0.44). GUSTO moderate or severe bleeding risk was increased with vorapaxar and was not significantly altered by planned thienopyridine (planned HR 1.50, 1.18-1.89, p<0.001; no planned HR 1.90, 1.17-3.07, p=0.009; p-interaction=0.37) or actual thienopyridine use (p-interaction=0.24).
Conclusions—Vorapaxar reduced cardiovascular death, MI, or stroke in stable patients with a history of prior MI, whether treated concomitantly with a thienopyridine or not. The relative risk of moderate or severe bleeding was similarly increased irrespective of thienopyridine use.
Clinical Trial Registration Information—http://www.clinicaltrials.gov. Identifier: NCT00526474
- Received December 23, 2014.
- Revision received August 26, 2015.
- Accepted August 31, 2015.