Background-Vorapaxar, a protease-activated receptor-1 antagonist, is approved for secondary prevention of cardiovascular events but is associated with increased intracranial hemorrhage. Methods and Results-TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) was a trial of vorapaxar versus placebo among patients with acute coronary syndrome. Strokes were adjudicated by a central events committee. Of 12 944 patients, 199 (1.5%) had ≥1 stroke during the study period (median follow-up, 477 days). Four patients had a single stroke of unknown type; 195 patients had ≥1 stroke classified as hemorrhagic or nonhemorrhagic (165 nonhemorrhagic, 28 hemorrhagic, and 2 both). Strokes occurred in 96 of 6473 patients (1.5%) assigned vorapaxar and 103 of 6471 patients (1.6%) assigned placebo. Kaplan-Meier incidence of stroke for vorapaxar versus placebo was higher for hemorrhagic stroke (0.45% versus 0.14% [hazard ratio, 2.74; 95% confidence interval, 1.22-6.15]), lower but not significantly different for nonhemorrhagic stroke (1.53% versus 1.98% at 2 years [hazard ratio, 0.79; 95% confidence interval, 0.58-1.07]), and similar for stroke overall (1.93% versus 2.13% at 2 years [hazard ratio, 0.94; 95% confidence interval, 0.71-1.24]). Conclusions-Stroke occurred in <2% of patients. Vorapaxar-assigned patients had increased hemorrhagic stroke but a nonsignificant trend toward lower nonhemorrhagic stroke. Overall stroke frequency was similar with vorapaxar versus placebo.
|Journal||Journal of the American Heart Association|
|State||Published - Dec 1 2018|
Bibliographical noteFunding Information:
research grants or contracts from Sanofi Aventis Recherche & Développement, Merck, Boehringer Ingelheim, Bayer, and CSL Limited; and consulting for AstraZeneca, Merck, Bayer, Novartis, and Boehringer Ingelheim. Aylward reports research grants from Merck & Co, AstraZeneca, Sanofi, and GSK; honoraria (speaker’s bureau and advisory board) from AstraZeneca, Eli Lilly, Boehringer Ingelheim, Bayer J&J, Servier, and Bristol Myers Squibb. Held reports institutional research grants from AstraZeneca, GlaxoSmithKline, Pfizer/Bristol Myers Squibb, Roche, and Schering-Plough (now Merck); and consulting for AstraZeneca. Moliterno reports grants from Merck, Inc, during the conduct of the study. Strony is a former employee of Merck & Co and a current employee of Johnson & Johnson. Van de Werf reports research grants, honoraria for lectures, and advisory board membership for Merck. Wallentin reports grants from Merck & Co and Roche Diagnostics; grants and personal fees from Bristol-Myers Squibb/Pfizer, AstraZeneca, GlaxoSmithKline, and Boehringer Ingelheim; and personal fees from Abbott. White reports grants from Sanofi Aventis, Eli Lilly and Company, National Institutes of Health (NIH), and DalGen Products and Services; personal fees and nonfinancial support from AstraZeneca; grants and personal fees from Omthera Pharmaceuticals, Pfizer, and Elsai Inc; and personal fees from Sirtex and Acetelion. Tricoci reports a consultant agreement and research grant from Merck. All disclosures are available at https://dcri.org/about-us/conflic t-of-interest/. Harrington reports consultant fees/honoraria from Adverse Events, Amgen Inc, Daiichi-Lilly, Gilead Sciences, Janssen Research and Development, Medtronic, Merck, Novartis Corporation, The Medicines Company, Vida Health, Vox Media, and WebMD; research/research grants from AstraZeneca, BMS, CSL Behring, GSK, Merck, Portola, Sanofi-Aventis, and The Medicines Company; ownership interest/partnership/principal from Element Science and MyoKardia; officer, director, trustee, or other fiduciary role for Evidint and Scanadu; Data Safety Monitoring Board for Regado; and other: American Heart Association. Mahaffey reports financial disclosures available at http://med.stanf ord.edu/profiles/kenneth-mahaffey; research grant or contract from Afferent, Amgen, Apple Inc, AstraZeneca, Cardiva Medical Inc, Daiichi, Ferring, Google (Verily), Johnson & Johnson, Luitpold, Medtronic, Merck, NIH, Novartis, Sanofi, St Jude, and Tenax; consulting for Abbott, Ablynx, AstraZeneca, Baim Institute, Boehringer Ingelheim, Bristol Myers Squibb, Cardiometabolic Health Congress, Elsevier, GlaxoSmithKline, Johnson & Johnson, Medergy, Medscape, Merck, Mitsubishi, Myokardia, NIH, Novartis, Novo Nordisk, Oculeve, Portola, Radiometer, Springer Publishing, Theravance, University of California, San Francisco, and WebMD; and equity in BioPrint Fitness. Melloni reports research grants or contracts from Abbott Laboratories, Amgen Inc, Duke Clinical Research Institute, Genzyme Corporation, Janssen Research & Development, Lundbeck Pharmaceuticals, Pfizer, and TESARO Inc; and consulting for Amgen Inc, Genetech, and Shire. A full list of disclosures for Dr Melloni is available at https://dcri. org/about-us/conflict-of-interest/. The remaining authors have no disclosures to report.
The TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) trial was funded by Merck & Co.
© 2018 The Authors.
- Acute coronary syndrome
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine