Key result
Cimlanod lowers stroke volume index by ~1 mL/m2 vs placebo, showing similar hemodynamics to nitroglycerin.
Why the study?
Nitroxyl causes vasodilatation and inotropic and lusitropic effects in animals, prompting comparison of the nitroxyl donor cimlanod against nitroglycerin or placebo on cardiac function in chronic HFrEF.
Does cimlanod improve stroke volume index compared to nitroglycerin or placebo in patients with stable HFrEF?
RCT (n=45)
double-blind
randomized
Yes
Does cimlanod improve stroke volume index compared to nitroglycerin or placebo in patients with stable HFrEF?
Absolute Event Rate: 29% vs 30%
p-value: p=0.03
In patients with stable HFrEF, the nitroxyl donor cimlanod produces similar hemodynamic effects to nitroglycerin, primarily through venodilation and preload reduction rather than inotropic effects.
Cimlanod matches nitroglycerin via preload reduction without added inotropy or lusitropy in stable HFrEF; challenges animal data and leaves open acute decompensated HF utility.
Aims Nitroxyl provokes vasodilatation and inotropic and lusitropic effects in animals via post‐translational modification of thiols. We aimed to compare effects of the nitroxyl 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, multicentre, 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 derived from the left ventricular outflow tract at the end of each infusion period. Stroke volume index with placebo was 30 ± 7 mL/m 2 and was lower with cimlanod (29 ± 9 mL/m 2 ; P = 0.03) and NTG (28 ± 8 mL/m 2 ; 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 haemodynamic 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.
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Lang et al. (2021) conducted an RCT in chronic heart failure with reduced ejection fraction (HFrEF) (n=45). cimlanod (BMS-986231) vs. nitroglycerin (NTG) or placebo was evaluated on stroke volume index derived from the left ventricular outflow tract at the end of each infusion period (p=0.03). A 5-hour intravenous infusion of cimlanod lowered stroke volume index compared to placebo (29 vs 30 mL/m2; P=0.03), demonstrating similar haemodynamic effects to nitroglycerin.
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