Nitroxyl (HNO) donors such as Cimlanod (BMS-986231/CXL-1427) have been investigated for potential vasodilatory, inotropic, and lusitropic effects in heart failure with reduced ejection fraction (HFrEF). This meta-analysis published in the American Journal of Cardiovascular Drugs included four studies comprising 459 patients (278 receiving Cimlanod; 181 placebo). The mean age was 63.9 years, 85% were male, and comorbidities included hypertension (77%) and diabetes (45.7%). Outcomes were analyzed using risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI).
Cimlanod did not significantly reduce all-cause mortality (RR 0.96; 95% CI 0.88–1.04; p=0.15), cardiac death (RR 0.75; 95% CI 0.37–1.54; p=0.43), overall adverse events (RR 1.51; 95% CI 0.94–2.44; p=0.073), or serious adverse events (RR 0.83; 95% CI 0.46–1.48; p=0.429) compared with placebo. Symptomatic hypotension was more frequent with Cimlanod (RR 2.22; 95% CI 1.56–3.15; p<0.01).
No significant pooled effect on systolic or diastolic blood pressure or heart rate was observed; however, the highest dose (12 μg/kg/min) was associated with a reduction in systolic blood pressure (MD −10.41; 95% CI −19.89 to −0.93).
Study quality followed Cochrane methods and the protocol was prospectively registered (PROSPERO CRD420250652675).
Cimlanod was not associated with improved mortality or major hemodynamic endpoints in pooled analyses. Further research is required to clarify potential subgroup effects.
