Key result
In-hospital initiation of sacubitril/valsartan was not associated with lower risk of HF rehospitalization or CV death compared with ARB therapy (HR 0.97; 95% CI 0.79-1.20).
Why the study?
The long-term real-world effectiveness and safety of in-hospital initiation of sacubitril/valsartan in patients hospitalized for acute HF with mildly reduced or preserved LVEF remain uncertain, especially among patients with advanced chronic kidney disease or dialysis.
Does in-hospital initiation of sacubitril/valsartan reduce HF rehospitalization or cardiovascular death compared to ARB therapy in patients with HFmrEF or HFpEF hospitalized for acute HF?
Cohort (n=9,107)
Yes
Does in-hospital initiation of sacubitril/valsartan reduce HF rehospitalization or cardiovascular death compared to ARB therapy in patients with HFmrEF or HFpEF hospitalized for acute HF?
In patients hospitalized for acute heart failure with LVEF >40%, in-hospital initiation of sacubitril/valsartan did not significantly improve long-term clinical outcomes compared to ARB therapy, despite greater biochemical improvement in NT-proBNP.
Answers are grounded in this paper and cite their sources.
No association with lower events for in-hospital sacubitril/valsartan versus ARBs; leaves open its benefit in acute HF with LVEF >40%.
BACKGROUND: The long-term real-world effectiveness and safety of in-hospital initiation of sacubitril/valsartan in patients hospitalized for acute heart failure (HF) with mildly reduced or preserved left ventricular ejection fraction (HFmrEF or HFpEF) remain uncertain, particularly among patients with advanced chronic kidney disease or dialysis, who are often underrepresented in randomized trials. PATIENTS/MATERIALS AND METHODS: We identified 9,107 patients with HFmrEF or HFpEF hospitalized for acute HF from the Chang Gung Research Database between January 1, 2016, and June 30, 2023. Propensity score weighting with overlap weights was applied to balance baseline characteristics between treatment groups. Risks of fatal and nonfatal outcomes were analyzed using Cox proportional hazards and Fine-Gray subdistribution hazard models, respectively. RESULTS: After overlap weighting, the incidence rates of the composite endpoint of HF rehospitalization and cardiovascular (CV) death were 39.7 and 40.3 per 100 person-years in the angiotensin receptor neprilysin inhibitor (ARNI) and angiotensin receptor blocker (ARB) groups, respectively (Hazard ratio, 0.97; 95% confidence interval, 0.79-1.20). In analyses stratified by chronic kidney disease stage, the association between treatment group and the primary endpoint was consistent among patients with eGFR ≥60, 30-59, <30 mL/min/1.73 m CONCLUSIONS: In this multi-institutional real-world cohort of patients hospitalized for acute HF with left ventricular ejection fraction (LVEF) >40%, in-hospital initiation of sacubitril/valsartan was not associated with lower risks of HF rehospitalization or CV death compared with ARB therapy, despite greater NT-proBNP reduction in a biomarker subcohort. Limited sample size precludes definitive conclusions regarding therapeutic equivalence. Message 1 In a real-world multi-institutional cohort of patients hospitalized for acute heart failure with left ventricular ejection fraction >40%, in-hospital initiation of sacubitril/valsartan was not associated with a significantly lower long-term risk of heart failure rehospitalization or cardiovascular death compared with ARB therapy.Message 2 Sacubitril/valsartan demonstrated a comparable safety profile to ARB therapy regarding worsening renal function and severe hyperkalemia, with consistent safety outcomes observed across all baseline renal function strata, including high-risk patients with advanced chronic kidney disease or those receiving dialysis.Message 3 Although sacubitril/valsartan led to a significantly greater reduction in NT-proBNP levels at 24 months compared to ARB therapy within an exploratory biomarker subcohort, this greater biochemical improvement did not translate into superior long-term clinical effectiveness.
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Huang et al. (2026) conducted a cohort in Acute heart failure with mildly reduced or preserved ejection fraction (n=9,107). Sacubitril/valsartan vs. Angiotensin receptor blocker (ARB) was evaluated on Composite of HF rehospitalization and cardiovascular (CV) death (HR 0.97, 95% CI 0.79-1.20). In-hospital initiation of sacubitril/valsartan was not associated with lower risk of HF rehospitalization or CV death compared with ARB therapy (HR 0.97; 95% CI 0.79-1.20).
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