Meta-analysis finds Cimlanod does not reduce mortality in HFrEF, increases hypotension riskCimlanod did not reduce death in heart failure patients

American journal of cardiovascular drugs : drugs, devices, and other interventions Published May 1, 2026 Study authors: Dandamudi Mrunalini, Ho Vinh Q T, Samaniego-Laguna Miguel A, Arrighini Giang Son, Chamay Salomon, Wa… PubMed ↗ DOI ↗ Editorial oversight: Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

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Key Takeaway

Consider that Cimlanod does not reduce mortality in HFrEF and increases symptomatic hypotension risk, limiting its routine use.

This meta-analysis evaluated the efficacy and safety of Cimlanod (BMS-986231, CXL-1427) in patients with heart failure with reduced ejection fraction (HFrEF). The analysis included 459 patients from available trials, comparing Cimlanod to placebo. The primary outcomes assessed were cardiovascular mortality, hemodynamic measures, and severe adverse events.

Key findings showed that Cimlanod did not significantly reduce all-cause mortality (RR 0.96; 95% CI 0.88-1.04; p = 0.15) or 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) and serious adverse events (RR 0.83; 95% CI 0.46-1.48; p = 0.429) were also not significantly different. However, symptomatic hypotension was significantly increased with Cimlanod (RR 2.22; 95% CI 1.56-3.15; p < 0.01). The highest dose caused a significant drop in systolic blood pressure (MD -10.41; 95% CI -19.89 to -0.93). No significant effects were observed on diastolic blood pressure or heart rate, while a modest improvement in cardiac index was noted.

Limitations include that the evidence does not currently support routine clinical use, and further studies are needed to identify potential subgroups that may benefit. The meta-analysis did not report follow-up duration or funding sources. Overall, the findings suggest a lack of mortality benefit and an increased risk of hypotension, limiting the drug's clinical utility.

A meta-analysis examined data from 459 patients with heart failure with reduced ejection fraction. The researchers compared the drug Cimlanod against a placebo to see if it improved survival or heart function. The study looked at cardiovascular mortality, hemodynamic measures, and severe adverse events. The analysis also checked all-cause mortality, cardiac death, and various blood pressure and heart rate readings.

The results showed that Cimlanod did not significantly reduce the risk of death from any cause. It also did not significantly reduce cardiac death or serious adverse events. However, the drug did significantly increase the risk of symptomatic hypotension, which is low blood pressure that causes symptoms. Patients taking the highest dose also saw a significant drop in systolic blood pressure.

The study noted a modest improvement in cardiac index, a measure of heart pumping ability. Despite these mixed findings, the evidence does not currently support routine clinical use of this medication. Further studies are required to identify whether any specific subgroup may benefit from the treatment.

What this means for you:

This meta-analysis found Cimlanod did not reduce death risk and increased low blood pressure symptoms in heart failure patients.

Study Details

Study typeMeta analysis

Sample sizen = 459

EvidenceLevel 1

PublishedMay 2026

PMID41686423

View Original Abstract ↓

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 I 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.

Meta-analysis finds Cimlanod does not reduce mortality in HFrEF, increases hypotension riskCimlanod did not reduce death in heart failure patients

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