Key result
Off-label sacubitril/valsartan shows no benefit for cardiovascular events or re-hospitalization in HF with ESKD.
Why the study?
Physician-guided dosing of sacubitril/valsartan according to kidney function is inconsistent in real-world practice, and the effects of off-label dosing on long-term clinical outcomes in heart failure patients with end-stage kidney disease require evaluation.
Does off-label real-world dosing of sacubitril/valsartan affect arrhythmic events, re-hospitalization, and cardiovascular events in patients with heart failure and end-stage kidney disease undergoing hemodialysis?
Cohort (n=379)
Does off-label real-world dosing of sacubitril/valsartan affect arrhythmic events, re-hospitalization, and cardiovascular events in patients with heart failure and end-stage kidney disease undergoing hemodialysis?
In patients with heart failure and end-stage kidney disease on hemodialysis, off-label dosing of sacubitril/valsartan did not significantly impact long-term clinical outcomes, whereas a PVC burden >2866.5 beats/24 hours was independently associated with decreased LVEF.
Off-label sacubitril/valsartan dosing should not alter prescribing in HF with ESKD; leaves open PVC burden as a potential LVEF modifier.
Background Sacubitril/Valsartan represent one of the cornerstone treatments to treat chronic heart failure with reduced ejection fraction. However, the choices of Sacubitril/Valsartan dose guided by the decision-making process of the physician, which considers specific according to kidney functions are inconsistent in the real-world practice. Objective The objective of the present study is to evaluate the effects of real-world Off-label dose of Sacubitril/Valsartan on long-term clinical outcomes in HF patients with end-stage kidney disease (ESKD). Methods Our database of HF patients diagnosed with ESKD from 2015 to 2025 was used to obtain laboratory, echocardiography, electrocardiogram (ECG), and clinical outcomes data. Inclusion criteria were all HF patients using Sacubitril/Valsartan with ESKD undergoing hemodialysis. And we compared arrhythmic events, re-hospitalization, and cardiovascular events according to LV ejection fraction (LVEF) change using off-label real -world dose of Sacubitril/Valsartan. Results Among 379 patients with HF and ESKD (75.1±11.9 years), 240 (63.5%) patients had LVEF improvement using Sacubitril/Valsartan. Difference in the baseline characteristics was not observed among patients. During the median 24-month follow-up, there was no significant difference of arrhythmic events, re-hospitalization, and cardiovascular events according to off-label real-world dose of Sacubitril/Valsartan (P=0.609). In multivariate analysis, lower incidence of premature ventricular complex (PVC) was independent risk factors for LVEF improvement events (OR 0.950; CI 0.908-0.983; P=0.032). Cut-off of PVC burden> 2866.5 beats/24 hours (Sensitivity 0.422; Specificity 0.966; AUC = 0.752; P=0.005) was associated with decreased LVEF. Conclusions There was no significant difference of arrhythmic events, re-hospitalization, and cardiovascular events according to off-label real-world dose of Sacubitril/Valsartan. Instead, PVC> 2866 beats/24 hours was independent risk factor for heart failure aggravationin HF patients with ESKD.figure 1ROC
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S I Im (2026) conducted a cohort in Heart failure and end-stage kidney disease (n=379). Off-label real-world dose of Sacubitril/Valsartan vs. Different off-label dosing groups / LVEF change groups was evaluated on Arrhythmic events, re-hospitalization, and cardiovascular events (p=0.609). Off-label Sacubitril/Valsartan dosing showed no significant difference in arrhythmic events, re-hospitalization, and cardiovascular events in HF patients with ESKD (P=0.609).
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