Impact of vasodilators on diuretic response in patients with congestive heart failure: a mechanistic trial of cimlanod (BMS‐986231)

Pellicori, P. et al. (2023) Impact of vasodilators on diuretic response in patients with congestive heart failure: a mechanistic trial of cimlanod (BMS‐986231). European Journal of Heart Failure, (doi: 10.1002/ejhf.3077) (PMID:37990754) (Early Online Publication)

Abstract

Background: Cimlanod is a nitroxyl donor with vasodilator properties. Methods: In this randomised, double-blind, mechanistic, cross-over trial, twenty-one patients with left ventricular ejection fraction <45%, increased plasma concentrations of NT-proBNP and receiving loop diuretics were given, on separate study days, either an eight-hour intravenous (IV) infusion of cimlanod (12 μg/kg/min) or placebo. Furosemide was given as a 40 mg IV bolus four hours after the start of infusion. The primary endpoint was urine volume in the four hours after the bolus of furosemide during infusion of cimlanod compared with placebo. Results: Median NT-proBNP at baseline was 1,487 (IQR: 847–2,665) ng/L. Infusion of cimlanod increased cardiac output and reduced blood pressure without affecting cardiac power index consistent with a vasodilator effect. Urine volume in the 4 hours post-furosemide was lower with cimlanod (1,032 ± 393 mL) versus placebo (1,481 ± 560 mL) (P = 0.002), as were total sodium excretion (P = 0.004), fractional sodium excretion (P = 0.016), systolic blood pressure (P < 0.001), estimated glomerular filtration rate (P = 0.012), and haemoglobin (P = 0.010), an index of plasma volume expansion. Conclusions: For patients with heart failure and congestion, vasodilation with agents such as cimlanod reduces the response to diuretic agents, which may offset any benefit from acute reductions in cardiac preload and afterload.

• Item Type: Articles
• Additional Information: Bristol Myers Squibb (ClinicalTrials.gov identifier: NCT03730961).
• Status: Early Online Publication
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Graham, Dr Fraser and Cleland, Professor John and McMurray, Professor John and Pellicori, Dr Pierpaolo
• Authors: Pellicori, P., Cleland, J. G.F., Borentain, M., Taubel, J., Graham, F., Khan, J., Bruzzese, D., Kessler, P., McMurray, J. J.V., Voors, A. A., O’Connor, C. M., Teerlink, J. R., and Felker, G. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > General Practice and Primary Care
• Journal Name: European Journal of Heart Failure
• Publisher: Wiley
• ISSN: 1388-9842
• ISSN (Online): 1879-0844
• Published Online: 21 November 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in European Journal of Heart Failure 2023
• Publisher Policy: Reproduced under a Creative Commons License