Renin-Angiotensin System Inhibition in Dialysis-Dependent Patients with Chronic Heart Failure due to Reduced Ejection Fraction: A Systematic Review and Meta-Analysis.

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.