William Schuyler Jones1, Pierluigi Tricoci2, Zhen Huang2, David J Moliterno3, Robert A Harrington4, Peter R Sinnaeve5, John Strony6, Frans Van de Werf5, Harvey D White7, Claes Held8, Paul W Armstrong9, Philip E Aylward10, Edmond Chen11, Manesh R Patel2, Kenneth W Mahaffey4. 1. Duke Clinical Research Institute, Duke University Medical Center, Durham, NC. Electronic address: schuyler.jones@dm.duke.edu. 2. Duke Clinical Research Institute, Duke University Medical Center, Durham, NC. 3. Gill Heart Institute and Division of Cardiovascular Medicine, University of Kentucky, Lexington, KY. 4. Department of Medicine, Stanford University, Stanford, CA. 5. Department of Cardiology, University of Leuven, Leuven, Belgium. 6. Merck & Co, Whitehouse Station, NJ. 7. Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand. 8. Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. 9. Division of Cardiology, University of Alberta, Edmonton, Canada. 10. South Australian Health and Medical Research Institute, Flinders University and Medical Centre, Adelaide, Australia. 11. Global Clinical Development, Bayer HealthCare Pharmaceuticals Inc, Whippany, NJ.
Abstract
BACKGROUND: In the TRACER trial, vorapaxar, a protease-activated receptor-1 antagonist, plus standard care in non-ST-segment elevation acute coronary syndrome (NSTE ACS) patients did not significantly reduce the primary composite end point but reduced a key secondary end point and significantly increased bleeding. History of peripheral artery disease (PAD) was a risk-enrichment inclusion criterion. We investigated the efficacy and safety of vorapaxar in NSTE ACS patients with documented PAD. METHODS: TRACER was a double-blind, randomized trial comparing vorapaxar with placebo in 12,944 patients with NSTE ACS. RESULTS: In total, 936 (7.2%) patients had a history of PAD. Ischemic events occurred more frequently among patients with PAD (25.3%) versus no PAD (12.2%, P < .001), and Global Use of Strategies to Open Occluded Coronary Arteries moderate/severe bleeding was more common in PAD (9.1%) versus no PAD (5.0%, P = .004). Similar rates of the composite end point (cardiovascular death, myocardial infarction, or stroke) occurred in patients with PAD treated withvorapaxar and placebo (21.7% vs 24.8%, P interaction = .787). Patients with PAD treated withvorapaxar, when compared with placebo, also had a numerical reduction in peripheral revascularization procedures (8.1% vs 9.0%, P = .158) and a lower extremity amputation rate (0.9% vs 1.5%, P = .107). Vorapaxar increased Global Use of Strategies to Open Occluded Coronary Arteries moderate/severe bleeding similarly in patients with PAD (hazard ratio 1.47, 95% CI 0.89-2.45) and without (hazard ratio 1.48, 95% CI 1.22-1.79; P interaction = .921). CONCLUSIONS: Patients with NSTE ACS and PAD were at increased risk for ischemic events. Lower rates of ischemic end points, peripheral revascularization, and amputation with vorapaxar did not reach statistical significance but warrant further investigation. Vorapaxar increased bleeding in both patients with and without PAD at a similar magnitude of risk.
RCT Entities:
BACKGROUND: In the TRACER trial, vorapaxar, a protease-activated receptor-1 antagonist, plus standard care in non-ST-segment elevation acute coronary syndrome (NSTE ACS) patients did not significantly reduce the primary composite end point but reduced a key secondary end point and significantly increased bleeding. History of peripheral artery disease (PAD) was a risk-enrichment inclusion criterion. We investigated the efficacy and safety of vorapaxar in NSTE ACSpatients with documented PAD. METHODS: TRACER was a double-blind, randomized trial comparing vorapaxar with placebo in 12,944 patients with NSTE ACS. RESULTS: In total, 936 (7.2%) patients had a history of PAD. Ischemic events occurred more frequently among patients with PAD (25.3%) versus no PAD (12.2%, P < .001), and Global Use of Strategies to Open Occluded Coronary Arteries moderate/severe bleeding was more common in PAD (9.1%) versus no PAD (5.0%, P = .004). Similar rates of the composite end point (cardiovascular death, myocardial infarction, or stroke) occurred in patients with PAD treated with vorapaxar and placebo (21.7% vs 24.8%, P interaction = .787). Patients with PAD treated with vorapaxar, when compared with placebo, also had a numerical reduction in peripheral revascularization procedures (8.1% vs 9.0%, P = .158) and a lower extremity amputation rate (0.9% vs 1.5%, P = .107). Vorapaxar increased Global Use of Strategies to Open Occluded Coronary Arteries moderate/severe bleeding similarly in patients with PAD (hazard ratio 1.47, 95% CI 0.89-2.45) and without (hazard ratio 1.48, 95% CI 1.22-1.79; P interaction = .921). CONCLUSIONS:Patients with NSTE ACS and PAD were at increased risk for ischemic events. Lower rates of ischemic end points, peripheral revascularization, and amputation with vorapaxar did not reach statistical significance but warrant further investigation. Vorapaxar increased bleeding in both patients with and without PAD at a similar magnitude of risk.
Authors: Maria Teresa B Abola; Jonathan Golledge; Tetsuro Miyata; Seung-Woon Rha; Bryan P Yan; Timothy C Dy; Marie Simonette V Ganzon; Pankaj Kumar Handa; Salim Harris; Jiang Zhisheng; Ramakrishna Pinjala; Peter Ashley Robless; Hiroyoshi Yokoi; Elaine B Alajar; April Ann Bermudez-Delos Santos; Elmer Jasper B Llanes; Gay Marjorie Obrado-Nabablit; Noemi S Pestaño; Felix Eduardo Punzalan; Bernadette Tumanan-Mendoza Journal: J Atheroscler Thromb Date: 2020-07-04 Impact factor: 4.928
Authors: Alexander C Fanaroff; Pratik Manandhar; David R Holmes; David J Cohen; J Kevin Harrison; G Chad Hughes; Vinod H Thourani; Michael J Mack; Matthew W Sherwood; W Schuyler Jones; Sreekanth Vemulapalli Journal: Circ Cardiovasc Interv Date: 2017-10 Impact factor: 6.546