Effect of ularitide on cardiovascular mortality in acute heart failure

Packer, M. et al. (2017) Effect of ularitide on cardiovascular mortality in acute heart failure. New England Journal of Medicine, 376(20), pp. 1956-1964. (doi: 10.1056/NEJMoa1601895) (PMID:28402745)

Abstract

Background: In patients with acute heart failure, early intervention with an intravenous vasodilator has been proposed as a therapeutic goal to reduce cardiac-wall stress and, potentially, myocardial injury, thereby favorably affecting patients' long-term prognosis. Methods: In this double-blind trial, we randomly assigned 2157 patients with acute heart failure to receive a continuous intravenous infusion of either ularitide at a dose of 15 ng per kilogram of body weight per minute or matching placebo for 48 hours, in addition to accepted therapy. Treatment was initiated a median of 6 hours after the initial clinical evaluation. The coprimary outcomes were death from cardiovascular causes during a median follow-up of 15 months and a hierarchical composite end point that evaluated the initial 48-hour clinical course. Results: Death from cardiovascular causes occurred in 236 patients in the ularitide group and 225 patients in the placebo group (21.7% vs. 21.0%; hazard ratio, 1.03; 96% confidence interval, 0.85 to 1.25; P=0.75). In the intention-to-treat analysis, there was no significant between-group difference with respect to the hierarchical composite outcome. The ularitide group had greater reductions in systolic blood pressure and in levels of N-terminal pro-brain natriuretic peptide than the placebo group. However, changes in cardiac troponin T levels during the infusion did not differ between the two groups in the 55% of patients with paired data. Conclusions: In patients with acute heart failure, ularitide exerted favorable physiological effects (without affecting cardiac troponin levels), but short-term treatment did not affect a clinical composite end point or reduce long-term cardiovascular mortality. (Funded by Cardiorentis; TRUE-AHF ClinicalTrials.gov number, NCT01661634.).

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Petrie, Professor Mark and McMurray, Professor John
• Authors: Packer, M., O'Connor, C., McMurray, J. J.V., Wittes, J., Abraham, W. T., Anker, S. D., Dickstein, K., Filippatos, G., Holcomb, R., Krum, H., Maggioni, A. P., Mebazaa, A., Peacock, W. F., Petrie, M. C., Ponikowski, P., Ruschitzka, F., van Veldhuisen, D. J., Kowarski, L. S., Schactman, M., and Holzmeister, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: New England Journal of Medicine
• Publisher: Massachusetts Medical Society
• ISSN: 0028-4793
• ISSN (Online): 1533-4406
• Published Online: 12 April 2017
• Copyright Holders: Copyright © 2017 Massachusetts Medical Society
• First Published: First published in New England Journal of Medicine 376(20): 1956-1964
• Publisher Policy: Reproduced in accordance with the publisher copyright policy