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Effects of Serelaxin in Patients with Acute Heart Failure

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posted on 27.08.2019, 16:11 by I Squire, M Metra, JR Teerlink, G Cotter, BA Davison, GM Felker, G Filippatos, BH Greenber, PS Pang, P Ponikowski, AA Voors, KF Adams, SD Anker
BACKGROUND Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. METHODS In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. RESULTS A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P=0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. CONCLUSIONS In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778. opens in new tab.)

Funding

Supported by Novartis Pharma. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. Drs. Metra and Teerlink contributed equally to this article. We thank Chien-Wei Chen (Novartis Pharmaceuticals) for statistical support, Vajhula Sarma (Novartis Healthcare) for graphical support, and Laoighse Mulrane (Novartis Ireland) for editorial logistics support.

History

Citation

New England Journal of Medicine, 2019, 381, pp. 716-726 (11)

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciences

Version

VoR (Version of Record)

Published in

New England Journal of Medicine

Publisher

Massachusetts Medical Society

issn

0028-4793

Acceptance date

03/05/2019

Copyright date

2019

Publisher version

https://www.nejm.org/doi/10.1056/NEJMoa1801291

Notes

The file associated with this record is under embargo until 6 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.

Language

en

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