• Erin A Bohula, Philip E Aylward, Marc P Bonaca, Ramon L Corbalan, Robert G Kiss, Sabina A Murphy, Benjamin M Scirica, Harvey White, Eugene Braunwald, and David A Morrow.
• From TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., M.P.B., S.A.M., B.M.S., E.B., D.A.M.); Department of Cardiovascular Medicine, Flinders Cardiovascular Center, Adelaide, Australia (P.E.A.); Cardiovascular Division, Pontificia Universidad Catolica de Chile, Santiago, Chile (R.L.C.); Department of Cardiology, Military Hospital, Budapest, Hungary (R.G.K.); and Green Lane Cardiovascular Research Unit, Auckland City Hospital, Auckland, New Zealand (H.W.). ebohula@partners.org.
• Circulation. 2015 Nov 17; 132 (20): 1871-9.

BackgroundVorapaxar antagonizes protease-activated receptor 1, the primary receptor for thrombin on human platelets, and reduces recurrent thrombotic events in stable patients with a previous 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 ResultsThe Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction 50 (TRA 2°P-TIMI 50) was a randomized, double-blind, placebo-controlled trial of vorapaxar in 26,449 patients with previous atherothrombosis. This prespecified 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 transient ischemic attack 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 in comparison with placebo regardless of planned thienopyridine therapy (planned thienopyridine, hazard ratio, 0.80, 0.70-0.91, P<0.001; no planned thienopyridine, hazard ratio, 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). Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) moderate or severe bleeding risk was increased with vorapaxar and was not significantly altered by planned thienopyridine (planned, hazard ratio, 1.50; 1.18-1.89, P<0.001; no planned, hazard ratio, 1.90, 1.17-3.07, P=0.009; P-interaction=0.37) or actual thienopyridine use (P-interaction=0.24).ConclusionsVorapaxar reduced cardiovascular death, MI, or stroke in stable patients with a history of previous 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 RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00526474.© 2015 American Heart Association, Inc.

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