BACKGROUND AND HYPOTHESIS:Evidence supporting renin-angiotensin system (RAS) inhibition in dialysis-dependent patients with heart failure with reduced ejection fraction (HFrEF) remains limited. We performed a systematic review and meta-analysis to assess the efficacy and safety of angiotensin receptor-neprilysin inhibitors (ARNIs) and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs) in this population (PROSPERO ID: CRD420251274393). METHODS:Outcomes of interest included all-cause mortality and cardiovascular mortality. Eligible studies included adult patients with chronic HFrEF on maintenance hemodialysis or peritoneal dialysis, comparing ARNI versus non-ARNI regimens and ACEi/ARB versus control regimens. Literature searches were conducted through December 2025 in PubMed, EMBASE, Google Scholar, and Web of Science. Hazard ratios (HRs) and their respective 95% confidence intervals (CIs) were pooled and meta-analyzed across studies. RESULTS:Overall, six studies evaluated ARNIs (3,818 treated; 4,344 controls), and three studies evaluated ACEi/ARBs (3,293 treated; 1,982 controls). ARNI use versus non-ARNI regimens was associated with significantly lower all-cause mortality (pooled HR 0.78, 95% CI 0.71-0.87), as was ACEi/ARB initiation versus placebo or no RAS blockade (pooled HR 0.76, 95% CI 0.68-0.84). ACEi/ARB therapy was also associated with lower cardiovascular mortality (pooled HR 0.62, 95% CI 0.54-0.71), whereas no significant association was observed with ARNIs (pooled HR 0.91, 95% CI 0.79-1.04). Safety data were available only for ARNI studies, suggesting no excess hypotension and a lower risk of hyperkalemia compared with ACEi/ARBs. CONCLUSIONS:In dialysis-dependent patients with HFrEF, ARNI use versus non-ARNI regimens, and ACEi/ARB use versus placebo or no RAS blockade, were each associated with lower all-cause mortality, while lower cardiovascular mortality was observed only with ACEi/ARB therapy. These findings suggest a potential overall benefit of RAS blockade in this population; however, they are derived predominantly from observational studies, remain susceptible to residual confounding and should not be interpreted as demonstrating causal treatment effects.

In advanced heart failure (AdHF), repeated levosimendan infusions between 0.1 and 0.2 μg/kg/min for 6–24 h every 2–4 weeks were associated with inconsistent outcomes and trends towards worse prognosis. Treatment effect with lower dosing is however unknown. The aims of this retrospective study were to assess the impact of 24-h levosimendan cycles at 0.05 μg/kg/min every 4 weeks on HF therapy, outcomes, and safety and to identify predictors of treatment efficacy. Among 286 AdHF patients, 39 levosimendan-treated subjects (4.19 ± 2.6 infusions) and 39 standard-of-care (SOC) subjects matched 1:1 based on a propensity score accounting for age, sex, ischemic heart disease, left ventricular (LV) ejection fraction, creatinine, heart rhythm, and heart transplantation (HTx) listing underwent comparison of their outcome. Efficacy was defined as 1-year survival without LV-assist-device, urgent HTx and urgent hospitalization for HF. Adverse events (AE) included permanent levosimendan interruption, sustained arrhythmias, or hypotension occasioning permanent infusion hold. Beta-blocker (BB) dose increased with levosimendan [34.7