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
Fatih Akkaya, Onur Osman Şeker, Ercan Türkmen, Seçkin DereliABSTRACT
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.