Effects of a novel nitroxyl donor in acute heart failure: the STAND-UP AHF Study

Felker, G. M. et al. (2020) Effects of a novel nitroxyl donor in acute heart failure: the STAND-UP AHF Study. JACC: Heart Failure, (doi: 10.1016/j.jchf.2020.10.012) (PMID:33248986) (In Press)

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Abstract

Objectives: The primary objective was to identify well-tolerated doses of cimlanod in patients with acute heart failure (AHF). Secondary objectives were to identify signals of efficacy, including biomarkers, symptoms, and clinical events. Background: Nitroxyl (HNO) donors have vasodilator, inotropic and lusitropic effects. Bristol-Myers Squibb-986231 (cimlanod) is an HNO donor being developed for acute heart failure (AHF). Methods: This was a phase IIb, double-blind, randomized, placebo-controlled trial of 48-h treatment with cimlanod compared with placebo in patients with left ventricular ejection fraction ≤40% hospitalized for AHF. In part I, patients were randomized in a 1:1 ratio to escalating doses of cimlanod or matching placebo. In part II, patients were randomized in a 1:1:1 ratio to either of the 2 highest tolerated doses of cimlanod from part I or placebo. The primary endpoint was the rate of clinically relevant hypotension (systolic blood pressure <90 mm Hg or patients became symptomatic). Results: In part I (n = 100), clinically relevant hypotension was more common with cimlanod than placebo (20% vs. 8%; relative risk [RR]: 2.45; 95% confidence interval [CI]: 0.83 to 14.53). In part II (n = 222), the incidence of clinically relevant hypotension was 18% for placebo, 21% for cimlanod 6 μg/kg/min (RR: 1.15; 95% CI: 0.58 to 2.43), and 35% for cimlanod 12 μg/kg/min (RR: 1.9; 95% CI: 1.04 to 3.59). N-terminal pro–B-type natriuretic peptide and bilirubin decreased during infusion of cimlanod treatment compared with placebo, but these differences did not persist after treatment discontinuation. Conclusions: Cimlanod at a dose of 6 μg/kg/min was reasonably well-tolerated compared with placebo. Cimlanod reduced markers of congestion, but this did not persist beyond the treatment period. (Evaluate the Safety and Efficacy of 48-Hour Infusions of HNO (Nitroxyl) Donor in Hospitalized Patients With Heart Failure [STANDUP AHF]; NCT03016325)

Item Type:Articles
Status:In Press
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lang, Dr Ninian and Cleland, Professor John and McMurray, Professor John
Authors: Felker, G. M., McMurray, J. J.V., Cleland, J. G., O’Connor, C. M., Teerlink, J. R., Voors, A. A., Belohlavek, J., Böhm, M., Borentain, M., Bueno, H., Cole, R. T., DeSouza, M. M., Ezekowitz, J. A., Filippatos, G., Lang, N., Kessler, P. D., Martinez, F. A., Mebazaa, A., Metra, M., Mosterd, A., Pang, P. S., Ponikowski, P., Sato, N., Seiffert, D., and Ye, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:JACC: Heart Failure
Publisher:Elsevier
ISSN:2213-1779
ISSN (Online):2213-1787
Published Online:25 November 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in JACC: Heart Failure 2020
Publisher Policy:Reproduced under a Creative Commons license

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