Does Cimlanod lower the chance of dying from heart failure with reduced ejection fraction?
Cimlanod (also known as BMS-986231 or CXL-1427) is an investigational nitroxyl donor that has been studied for heart failure with reduced ejection fraction (HFrEF). However, a meta-analysis of four clinical trials found that Cimlanod did not significantly reduce all-cause mortality or cardiac death compared to placebo. The drug also increased the risk of hypotension. Therefore, current evidence does not support that Cimlanod lowers the chance of dying from HFrEF.
What the research says
A meta-analysis published in 2025 pooled data from four randomized controlled trials involving 459 patients with HFrEF (278 received Cimlanod, 181 received placebo). The analysis found that Cimlanod did not significantly reduce all-cause mortality (risk ratio [RR] = 0.96; 95% confidence interval [CI] 0.88 to 1.04; p = 0.15) or cardiac death (RR = 0.75; 95% CI 0.37 to 1.54; p = 0.43) 5. These results indicate no clear survival benefit with Cimlanod.
Additionally, Cimlanod was associated with a higher risk of hypotension (RR = 2.82; 95% CI 1.40 to 5.68; p = 0.004) and a trend toward more adverse events (RR = 1.51; 95% CI 0.94 to 2.44; p = 0.073) 5. The drug's hemodynamic effects, including vasodilation and increased heart rate, may contribute to these side effects.
Other treatments for HFrEF, such as SGLT2 inhibitors (e.g., sotagliflozin) and the traditional Chinese medicine Qiliqiangxin, have shown significant reductions in cardiovascular death or heart failure hospitalization in clinical trials 128. In contrast, Cimlanod has not demonstrated such benefits in the available studies.
It is important to note that the meta-analysis included a relatively small number of patients and had limited statistical power to detect small differences in mortality. Larger trials would be needed to definitively rule out any potential benefit, but the current evidence does not support a mortality reduction with Cimlanod.
What to ask your doctor
- What are the current guideline-directed medical therapies for HFrEF that have proven survival benefits?
- Should I consider any investigational treatments like Cimlanod, and what are the potential risks (e.g., hypotension)?
- How do the risks and benefits of Cimlanod compare to other HFrEF medications I am taking?
- Are there any ongoing clinical trials for Cimlanod or similar drugs that I might be eligible for?
- What should I do if I experience symptoms of low blood pressure while on any heart failure treatment?
This question is drawn from common patient questions about this topic and answered using cited medical research. We do not provide individualized advice.