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Published on: February 13, 2021
Cimlanod, a Second-Generation Nitroxyl Donor, in Heart Failure with Reduced Ejection Fraction: A Meta-Analysis of
Mrunalini Dandamudi1, Vinh Q T Ho2, Miguel A Samaniego-Laguna3
1Montefiore Einstein Medical Center, 111 E 210th St, Bronx, NY, 10467, USA. mdandamudi@montefiore.org.
Insights
Cimlanod did not improve mortality or key heart failure metrics in patients with reduced ejection fraction. The drug increased the risk of symptomatic hypotension, suggesting it is not currently recommended for routine use.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Heart failure (HF) presents a significant global health challenge.
- Nitroxyl (HNO) donors, like Cimlanod, show potential for HF treatment due to vasodilatory properties.
Purpose of the Study:
- To evaluate the safety, tolerability, and hemodynamic impact of Cimlanod in patients with heart failure with reduced ejection fraction (HFrEF).
Main Methods:
- A meta-analysis of four studies involving 459 patients (278 on Cimlanod, 181 on placebo).
- Evaluated outcomes including mortality, adverse events, and hemodynamic measures.
- Study quality assessed using Cochrane methods; protocol registered on PROSPERO.
Main Results:
- Cimlanod did not significantly reduce all-cause mortality, cardiac death, or adverse events compared to placebo.
- A significant increase in symptomatic hypotension risk was observed (RR=2.22).
- A significant drop in systolic blood pressure was noted at the highest Cimlanod dose.
Conclusions:
- Cimlanod did not demonstrate efficacy in improving mortality or major hemodynamic endpoints in HFrEF patients.
- The drug increased the risk of symptomatic hypotension.
- Current evidence does not support routine Cimlanod use; further research is needed for specific subgroups.
Introduction:
Heart failure (HF), a leading cause of morbidity and mortality worldwide, continues to pose a therapeutic challenge. Nitroxyl (HNO) donors, such as Cimlanod (BMS-986231 or CXL-1427), are emerging as promising agents owing to their unique vasodilatory, inotropic, and lusitropic properties.
Purpose:
This meta-analysis assesses the safety, tolerability, and hemodynamic effects of Cimlanod, in patients with heart failure with reduced ejection fraction (HFrEF).
Methods:
This study consists of four studies, including 459 patients (278 receiving Cimlanod and 181 receiving placebo). The mean age was 63.9 years, 85% were male, and common comorbidities included hypertension (77%) and diabetes (45.7%). Outcomes were evaluated using risk ratios (RR) for binary end points and mean differences (MD) for continuous variables, with 95% confidence intervals (CI) and I2 for heterogeneity. Study quality followed Cochrane methods. Primary outcomes included cardiovascular mortality, hemodynamic measures, and severe adverse events. The protocol was prospectively registered in PROSPERO (CRD420250652675; Feb 2025).
Results:
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), 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), when compared with placebo. Although a significantly increased risk of symptomatic hypotension was observed with the use of Cimlanod (RR = 2.22; 95% CI 1.56-3.15; p < 0.01) but no significant effect on systolic or diastolic blood pressure or heart rate was observed in the pooled analyses, whereas significant drop in systolic blood pressure (SBP) (MD - 10.41, 95% CI - 19.89 to - 0.93) was observed with highest dose of Cimlanod i.e. 12 μcg/kg/min.
Conclusions:
Cimlanod did not improve mortality, major hemodynamic end points, or biomarkers and increased the risk of symptomatic hypotension. Although a modest improvement in cardiac index was observed, evidence does not currently support routine clinical use, and further studies are required to identify whether any specific subgroup may benefit.
Registration:
PROSPERO identifier number CRD420250652675.
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