Renin-Angiotensin System Inhibition in Dialysis-Dependent Patients with Chronic Heart Failure due to Reduced Ejection Fraction: A Systematic Review and Meta-Analysis
Aarthiga Sritharan, Matteo Marchetti, Panagiotis Antiochos, Léa Iten, Menno Pruijm, Philippe Meyer, Pierre Monney, Thibaut Charlemagne, Baris Gencer, Olivier Muller, Patrick Yerly, Roger Hullin, Henri LuAbstract
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.