Long-Term Renal Function and Clinical Outcomes of Sacubitril/Valsartan in HFrEF and Stage 3-4 Chronic Kidney Disease: A 24-Month Single-Centre Cohort.

BACKGROUND: Stage 3-4 chronic kidney disease (CKD) is common in heart failure with reduced ejection fraction (HFrEF) but remains underrepresented in angiotensin receptor-neprilysin inhibitor (ARNI) trials, fostering reluctance to initiate sacubitril/valsartan (S/V). HYPOTHESIS: We hypothesized that, over 24 months, S/V would be associated with stable renal function and acceptable clinical outcomes; the study was designed to be descriptive rather than comparative. METHODS: We retrospectively analyzed 360 adults with HFrEF (LVEF < 40%) and predialysis stage 3-4 CKD who initiated S/V (2017-2023) and were followed for up to 24 months; decedents were analyzed as events, not excluded. The primary renal composite (sustained ≥ 30% eGFR decline, chronic dialysis, or end-stage kidney disease) was analyzed with competing-risk methods (Aalen-Johansen and Fine-Gray, with death competing); mortality with Cox regression; longitudinal eGFR with mixed-effects; and sparse-event models with Firth penalization. RESULTS: Among survivors, mean eGFR was stable (mixed-model slope non-significant), with no creatinine rise; NT-proBNP and CRP fell (both p < 0.001) and NYHA class improved. The renal composite occurred in 12/360 (3.3%); all-cause and cardiovascular mortality were 6.1% and 3.9%. Lower baseline eGFR was associated with the renal composite. Analyzes of maintenance dose and concomitant SGLT2-inhibitor use were confounded by treatment tolerance and calendar era and were hypothesis-generating only. CONCLUSIONS: In this single-arm cohort of HFrEF with stage 3-4 CKD, S/V was generally well tolerated, with stable renal function and low event rates over 24 months. These descriptive, hypothesis-generating findings cannot establish comparative benefit and require confirmation in controlled studies.