Marc P Bonaca1, Benjamin M Scirica2, Eugene Braunwald2, Stephen D Wiviott2, Michelle L O'Donoghue2, Sabina A Murphy2, David A Morrow2. 1. TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: mbonaca@partners.org. 2. TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Abstract
BACKGROUND:Vorapaxar, a novel thrombin receptor antagonist, reduces cardiovascular death and recurrent thrombotic events when added to standard antiplatelet therapy in patients with stable atherosclerotic vascular disease. OBJECTIVES: The goal of this study was to test the hypothesis that treatment with vorapaxar reduces the rate of coronary stent thrombosis (ST) in stable patients with a history of coronary stenting. METHODS: TRA 2° P-TIMI 50 (Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients With Atherosclerosis-Thrombolysis In Myocardial Infarction 50) was a multinational, randomized, double-blind, placebo-controlled trial of vorapaxar in stable patients with prior myocardial infarction, peripheral arterial disease, or stroke. We evaluated the rates of definite ST as adjudicated by a central events committee using Academic Research Consortium (ARC) criteria. RESULTS: A total of 26,449 patients were randomized, with 14,042 (53%) having a history of a coronary stent implantation before randomization, and an additional 449 patients receiving a coronary stent during the trial (total 14,491). During follow-up (median 2.5 years), there were 152 definite ST events, with the majority (92%) occurring late or very late. Vorapaxar reduced ARC definite ST (1.1% vs. 1.4%, hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.51 to 0.98; p = 0.037). The reduction was consistent, regardless of time from percutaneous coronary intervention, history of diabetes, use of drug-eluting stents, and use of dual antiplatelet therapy (DAPT) at randomization. Vorapaxar increased GUSTOmoderate/severe bleeding (HR: 1.57, 95% CI: 1.26 to 1.94; p < 0.001). CONCLUSIONS: The rate of ARC definite ST in stable patients, the majority of whom were receiving DAPT, was approximately 1.4% at 3 years. In stable patients with coronary stenting receiving standard antiplatelet therapy, vorapaxar administered for long-term secondary prevention significantly reduced ARC definite ST, including very late ST. (Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Patients With Atherosclerosis [TRA 2° P-TIMI 50] [P04737]; NCT00526474).
RCT Entities:
BACKGROUND:Vorapaxar, a novel thrombin receptor antagonist, reduces cardiovascular death and recurrent thrombotic events when added to standard antiplatelet therapy in patients with stable atherosclerotic vascular disease. OBJECTIVES: The goal of this study was to test the hypothesis that treatment with vorapaxar reduces the rate of coronary stent thrombosis (ST) in stable patients with a history of coronary stenting. METHODS: TRA 2° P-TIMI 50 (Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients With Atherosclerosis-Thrombolysis In Myocardial Infarction 50) was a multinational, randomized, double-blind, placebo-controlled trial of vorapaxar in stable patients with prior myocardial infarction, peripheral arterial disease, or stroke. We evaluated the rates of definite ST as adjudicated by a central events committee using Academic Research Consortium (ARC) criteria. RESULTS: A total of 26,449 patients were randomized, with 14,042 (53%) having a history of a coronary stent implantation before randomization, and an additional 449 patients receiving a coronary stent during the trial (total 14,491). During follow-up (median 2.5 years), there were 152 definite ST events, with the majority (92%) occurring late or very late. Vorapaxar reduced ARC definite ST (1.1% vs. 1.4%, hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.51 to 0.98; p = 0.037). The reduction was consistent, regardless of time from percutaneous coronary intervention, history of diabetes, use of drug-eluting stents, and use of dual antiplatelet therapy (DAPT) at randomization. Vorapaxar increased GUSTO moderate/severe bleeding (HR: 1.57, 95% CI: 1.26 to 1.94; p < 0.001). CONCLUSIONS: The rate of ARC definite ST in stable patients, the majority of whom were receiving DAPT, was approximately 1.4% at 3 years. In stable patients with coronary stenting receiving standard antiplatelet therapy, vorapaxar administered for long-term secondary prevention significantly reduced ARC definite ST, including very late ST. (Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Patients With Atherosclerosis [TRA 2° P-TIMI 50] [P04737]; NCT00526474).
Authors: Eitan A Friedman; Luisa Texeira; Jessica Delaney; Peter E Weeke; Donald R Lynch; Ehab Kasasbeh; Yanna Song; Frank E Harrell; Josh C Denny; Heidi E Hamm; Dan M Roden; John H Cleator Journal: J Thromb Thrombolysis Date: 2016-05 Impact factor: 2.300
Authors: Stephen K Kidd; Marc P Bonaca; Eugene Braunwald; Gaetano M De Ferrari; Basil S Lewis; Piera A Merlini; Sabina A Murphy; Benjamin M Scirica; Harvey D White; David A Morrow Journal: J Am Heart Assoc Date: 2016-07-18 Impact factor: 5.501
Authors: Andrew M Veitch; Geoffroy Vanbiervliet; Anthony H Gershlick; Christian Boustiere; Trevor P Baglin; Lesley-Ann Smith; Franco Radaelli; Evelyn Knight; Ian M Gralnek; Cesare Hassan; Jean-Marc Dumonceau Journal: Gut Date: 2016-03 Impact factor: 23.059