Haemodynamic effects of the nitroxyl donor cimlanod (BMS-986231) in chronic heart failure: a randomized trial

Lang, N. N. et al. (2021) Haemodynamic effects of the nitroxyl donor cimlanod (BMS-986231) in chronic heart failure: a randomized trial. European Journal of Heart Failure, 23(7), pp. 1147-1155. (doi: 10.1002/ejhf.2138) (PMID:33620131)

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Abstract

Aims: Nitroxyl (HNO) provokes vasodilatation and inotropic and lusitropic effects in animals via post‐translational modification of thiols. We aimed to compare effects of the HNO donor cimlanod (BMS‐986231) with those of nitroglycerin (NTG) or placebo on cardiac function in patients with chronic heart failure with reduced ejection fraction (HFrEF). Methods and Results: In a randomized, multicenter, double‐blind, crossover trial, 45 patients with stable HFrEF were given a 5‐h intravenous infusion of cimlanod, NTG, or placebo on separate days. Echocardiograms were done at the start and end of each infusion period and read in a core laboratory. The primary endpoint was stroke volume index (SVI) derived from the left ventricular outflow tract at the end of each infusion period. SVI with placebo was 30±7 ml/m2 and was lower with cimlanod (29±9 ml/m2; p = 0.03) and NTG (28±8 ml/m2; p = 0.02). Transmitral E‐wave Doppler velocity on cimlanod or NTG was lower than on placebo and, consequently, E/e’ (p = 0.006) and E/A ratio (p = 0.003) were also lower. NTG had similar effects to cimlanod on these measurements. Blood pressure reduction was similar with cimlanod and NTG and greater than with placebo. Conclusion: In patients with chronic HFrEF, the hemodynamic effects of cimlanod and NTG are similar. The effects of cimlanod may be explained by venodilatation and preload reduction without additional inotropic or lusitropic effects. Ongoing trials of cimlanod will further define its potential role in the treatment of heart failure.

Item Type:Articles
Additional Information:This work was funded by Bristol-Myers Squibb (Princeton, NJ, USA).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lang, Dr Ninian and Cleland, Professor John and Ahmad, Dr Faheem and McMurray, Professor John
Authors: Lang, N. N., Ahmad, F. A., Cleland, J. G., O'Connor, C. M., Teerlink, J. R., Voors, A. A., Taubel, J., Hodes, A. R., Anwar, M., Karra, R., Sakata, Y., Ishihara, S., Senior, R., Khemka, A., Prasad, N. G., DeSouza, M. M., Seiffert, D., Ye, J. Y., Kessler, P. D., Borentain, M., Solomon, S. D., Felker, G. M., and McMurray, J. J.V.
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:European Journal of Heart Failure
Publisher:Wiley
ISSN:1388-9842
ISSN (Online):1879-0844
Published Online:23 February 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in European Journal of Heart Failure 23(7): 1147-1155
Publisher Policy:Reproduced under a Creative Commons License

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