Coronary Stent Thrombosis With Vorapaxar Versus Placebo

Fro Me sig pe No Me Ba My con Bri dio 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 InMyocardial Infarction50)wasamultinational, 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 1⁄4 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) (J Am Coll Cardiol 2014;64:2309–17) © 2014 by the American College of Cardiology Foundation. m the TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital and Harvard dical School, Boston, Massachusetts. This study was supported by a grant fromMerck & Co. The TIMI Study Group has received nificant research grant support from Accumetrics, Amgen, AstraZeneca, Beckman Coulter, Bristol-Myers Squibb, CV Therautics, Daiichi-Sankyo Co. Ltd., Eli Lilly and Company, GlaxoSmithKline, Integrated Therapeutics, Merck & Co., Nanosphere, vartis Pharmaceuticals, Nuvelo, Ortho-Clinical Diagnostics, Pfizer, Roche Diagnostics, Sanofi, Sanofi-Synthelabo, Siemens dical Solutions, and Singulex. Dr. Bonaca has received consulting fees from Roche Diagnostics, Merck & Co., AstraZeneca, and yer. Dr. Scirica has received research grants via the TIMI Study and Brigham and Women’s Hospital from AstraZeneca, Bristolers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Johnson & Johnson, Bayer Healthcare, Gilead, Eisai, and Merck & Co.; and sulting fees from AstraZeneca, GE Healthcare, Gilead, Lexicon, Arena, Eisai, St. Jude’s Medical, Forest Pharmaceuticals, stol-Myers Squibb, Boston Clinical Research Institute, Covance, University of Calgary, and Elsevier Practice Update Carlogy. Dr. Braunwald has received research grants (institutional) fromDaiichi-Sankyo, DukeUniversity, AstraZeneca,Merck&Co., ABBR EV I A T I ON S