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

Pierpaolo Pellicori, John G.F. Cleland*, Maria Borentain, Jorg Taubel, Fraser J. Graham, Javed Khan, Dario Bruzzese, Paul Kessler, John J.V. McMurray, Adriaan A. Voors, Christopher M. O'Connor, John R. Teerlink, G. Michael Felker

*Corresponding author voor dit werk

OnderzoeksoutputAcademicpeer review

4 Citaten (Scopus)
52 Downloads (Pure)


Aim: To investigate the effects of Cimlanod, a nitroxyl donor with vasodilator properties, on water and salt excretion after an administration of an intravenos bolus of furosemide. 

Methods and results: In this randomized, double-blind, mechanistic, crossover trial, 21 patients with left ventricular ejection fraction <45%, increased plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and receiving loop diuretics were given, on separate study days, either an 8 h 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 4 h after the bolus of furosemide during infusion of cimlanod compared with placebo. Median NT-proBNP at baseline was 1487 (interquartile range: 847–2665) ng/L. Infusion of cimlanod increased cardiac output and reduced blood pressure without affecting cardiac power index consistent with its vasodilator effects. Urine volume in the 4 h post-furosemide was lower with cimlanod (1032 ± 393 ml) versus placebo (1481 ± 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, vasodilatation with agents such as cimlanod reduces the response to diuretic agents, which may offset any benefit from acute reductions in cardiac preload and afterload.

Originele taal-2English
Pagina's (van-tot)142-151
Aantal pagina's10
TijdschriftEuropean Journal of Heart Failure
Nummer van het tijdschrift1
Vroegere onlinedatum21-nov.-2023
StatusPublished - jan.-2024


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