The effectiveness and safety of sacubitril/valsartan in real-world dialysis patients with heart failure reduced ejection fraction

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.