ARNI use in dialysis-dependent patients with HFrEF was associated with lower all-cause mortality compared to non-ARNI regimens (HR 0.78; 95% CI 0.71-0.87).
Meta-Analysis (n=13,437)
Do ARNIs and ACEi/ARBs reduce all-cause and cardiovascular mortality in dialysis-dependent patients with HFrEF?
RAS blockade with ARNIs or ACEi/ARBs is associated with improved survival in dialysis-dependent HFrEF patients, though current evidence is largely observational.
Hazard Ratio: 0.78 (95% CI 0.71–0.87)
Abstract 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.
Sritharan et al. (Wed,) conducted a meta-analysis in Chronic heart failure with reduced ejection fraction (HFrEF) on dialysis (n=13,437). Angiotensin receptor-neprilysin inhibitors (ARNIs) and ACEi/ARBs vs. Non-ARNI regimens, placebo, or no RAS blockade was evaluated on All-cause mortality (HR 0.78, 95% CI 0.71-0.87). ARNI use in dialysis-dependent patients with HFrEF was associated with lower all-cause mortality compared to non-ARNI regimens (HR 0.78; 95% CI 0.71-0.87).