Cimlanod did not significantly affect all-cause mortality (RR 0.85; 95% CI 0.30-2.39; P=0.29) but modestly lowered systolic blood pressure and increased the risk of symptomatic hypotension.
Meta-Analysis
Does Cimlanod improve hemodynamic effects and safety in patients with HFrEF?
In patients with HFrEF, the nitroxyl donor Cimlanod reduces systolic blood pressure but increases the risk of symptomatic hypotension without significantly affecting mortality or serious adverse events.
Relative Risk: 0.85 (95% CI 0.3–2.39)
valor p: p=0.29
Abstract Introduction Heart failure (HF), a leading cause of morbidity and mortality worldwide, continues to pose a therapeutic challenge. Nitroxyl (HNO) donors are emerging as promising agents, due to their unique vasodilatory, inotropic, and lusitropic properties. This meta-analysis synthesizes evidence from 4 pivotal studies investigating the safety and hemodynamic effects of Cimlanod in this population. Purpose This meta-analysis evaluates the safety, tolerability, and hemodynamic effects of Cimlanod, a HNO donor, in heart failure patients with reduced ejection fraction (HFrEF). Methods Multiple database searches were used to conduct a systematic review and meta-analysis of placebo-controlled, randomised trials of HNO donors in patients with HFrEF. Data were reported as Risk Ratio (RR), Mean difference (MD), and 95% confidence interval. Quality assessment was performed according to Cochrane recommendations. The primary endpoints of interest included cardiovascular mortality, hemodynamic effects, and adverse events. Results A pooled analysis of four studies reveals that NO donors reduce mean heart rate (MD=0.07; 95% CI: -2.83, -2.97; p=0.96; I²=0%), while modestly lowering systolic blood pressure (MD=-10.40; 95% CI: -19.89, -0.92; p=0.031; I²=88%) at the highest dose of 12mcg/kg/min. However, their effect on all-cause mortality (RR=0.85; 95% CI: 0.30, 2.39; p=0.29; I²=0%) is insignificant, and they are associated with an increased risk of symptomatic hypotension (RR=2.30; 95% CI: 1.01, 5.19; p=0.048; I²=0%). Serious adverse events (RR=0.81; 95% CI: 0.49, 1.34; p=0.28; I²=0%) show a non-significant trend toward reduction in the treatment group, though the confidence interval is wide, indicating uncertainty in the estimate. Other adverse events (RR=1.75, 95% CI: 0.61, 5.3; p=0.024; I²=68%) represent a significant reduction in the Cimlanod group but with high heterogeneity and remain comparable to placebo. These findings highlight the potential role of NO donors in heart rate modulation, necessitating careful monitoring to mitigate hypotensive risks. Conclusion Overall, the intervention effectively reduces heart rate, highlighting its potential benefits for tachyarrhythmias. However, it carries an increased risk of hypotension, which can be managed through dose adjustments and considered in clinical decisions. While no significant effects on mortality or major adverse events have been found, careful individual use with appropriate monitoring is advised. Although the treatment appears safe, additional studies with larger sample sizes must validate these findings.Graphical abstract Forest Plots
Dandamudi et al. (Sat,) conducted a meta-analysis in Heart failure with reduced ejection fraction (HFrEF). Cimlanod vs. Placebo was evaluated on All-cause mortality (RR 0.85, 95% CI 0.30-2.39, p=0.29). Cimlanod did not significantly affect all-cause mortality (RR 0.85; 95% CI 0.30-2.39; P=0.29) but modestly lowered systolic blood pressure and increased the risk of symptomatic hypotension.