Key result
Sacubitril/valsartan improves LVEF but fails to reduce mortality or HHF in advanced CKD and ESRD.
Why the study?
The impact of sacubitril/valsartan on advanced chronic kidney disease or end-stage renal disease remains unclear because these patients were excluded from major trials.
Does sacubitril/valsartan reduce all-cause mortality and heart failure hospitalization in adults with HFrEF and advanced CKD or ESRD requiring maintenance dialysis?
Meta-Analysis (n=4,329)
Does sacubitril/valsartan reduce all-cause mortality and heart failure hospitalization in adults with HFrEF and advanced CKD or ESRD requiring maintenance dialysis?
Odds Ratio: 0.54 (95% CI 0.25–1.18)
p-value: p=0.12
In patients with HFrEF and advanced CKD or ESRD, sacubitril/valsartan did not significantly reduce mortality or heart failure hospitalizations but significantly improved LVEF and reduced systolic blood pressure without increasing hyperkalemia or hypotension.
Backgrounds: Sacubitril/valsartan (angiotensin receptor neprilysin inhibitor [ARNi]) effectively treats heart failure with reduced ejection fraction. Its impact on advanced chronic kidney disease (CKD) or end-stage renal disease (ESRD) remains unclear due to their exclusion from major trials. We aimed to evaluate ARNi’s effectiveness and safety in these populations. Methods: We systematically searched PubMed, Cochrane, Embase, and ClinicalTrials.gov for observational studies of ARNi use in adults with advanced CKD or ESRD requiring maintenance dialysis. Primary outcomes were all-cause mortality and heart failure hospitalization (HHF), with secondary outcomes focusing on left ventricular ejection fraction (LVEF), blood pressure, and biomarkers. A random-effects model was used to derive pooled estimates, and study quality was assessed using the Newcastle-Ottawa scale. Results: Ten observational studies included 4329 patients with advanced CKD or ESRD. The pooled odds ratio (OR) for mortality plus HHF was 0.54 (95% confidence interval [CI]: 0.25–1.18, P = .12). Subgroup analysis showed ORs of 0.67 (95% CI: 0.17–2.70) for ESRD and 0.64 (95% CI: 0.25–1.66) for CKD. The pooled OR for mortality alone was 0.86 (95% CI: 0.50–1.46, P = .57). In ESRD, ARNi was linked to significant LVEF improvement (+4.20%, P < .001) and reduced systolic blood pressure (−7.13 mm Hg, P = .008), without increased risk of hyperkalemia or hypotension. Conclusion: In advanced CKD and ESRD with heart failure with reduced ejection fraction, ARNi did not significantly reduce mortality or HHF but showed potential benefit in LVEF improvement. Larger randomized trials are required to confirm its efficacy and safety in this high-risk population.
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Tu et al. (2026) conducted a meta-analysis in advanced chronic kidney disease (CKD) or end-stage renal disease (ESRD) with heart failure reduced ejection fraction (n=4,329). Sacubitril/valsartan was evaluated on all-cause mortality and heart failure hospitalization (HHF) (OR 0.54, 95% CI 0.25-1.18, p=0.12). Sacubitril/valsartan did not significantly reduce mortality or heart failure hospitalization in patients with advanced CKD or ESRD and HFrEF (OR 0.54; 95% CI 0.25-1.18; P=0.12).
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