Abstract 18595: Efficacy of Vorapaxar is not Modified by Thienopyridine Therapy: Results from TRA 2°P-TIMI 50 Trial
Vorapaxar antagonizes the platelet protease-activated receptor (PAR)-1,the primary receptor for thrombin on human platelets. The addition of vorapaxar to standard therapy has been shown to reduce thrombotic events in patients with stable atherosclerosis. We investigated whether the efficacy and safety of vorapaxar in stable atherosclerosis were modified by thienopyridine therapy. METHODS: The TRA2P-TIMI 50 trial was a randomized, double-blind, placebo controlled trial of vorapaxar 2.5 mg daily in 26,449 patients with established atherosclerotic vascular disease. Patients were stratified at randomization based on planned use of thienopyridine therapy. The first efficacy endpoint was a composite of cardiovascular death (CVD), MI, or stroke and the primary safety endpoint was GUSTO moderate or severe bleeding. Analyses were adjusted for qualifying disease state (MI, stroke, PAD). Treatment with ASA ≤ 162 mg was recommended. RESULTS: Thienopyridine was planned in 15,356 (58%) and ASA was used in 24,734 (94%) overall. Patients randomized to vorapaxar had similar significant reductions in the primary endpoint regardless of planned thienopyridine therapy (Figure, p-interaction 0.64) and after adjustment for qualifying disease state (MI, stroke, PAD). Findings were similar when patients were stratified by actual thienopyridine use at baseline (Figure, p-interaction 0.76) and at 18 months (p-interaction 0.99). GUSTO moderate or severe bleeding was increased with vorapaxar with no significant interaction in those planned for thienopyridine therapy (p-interaction 0.29) or those receiving thienopyridines through 18 months (p-interaction 0.71). CONCLUSIONS: Vorapaxar reduced CVD, MI, or stroke in stable patients with a history of atherothrombotic events and this effect was present whether or not vorapaxar was used with a thienopyridine. The increased risk of bleeding with vorapaxar was also similar regardless of thienopyridine therapy.
- © 2012 by American Heart Association, Inc.