Key result
Achieving ≥50% target sacubitril/valsartan dose is linked to ~60% fewer major events in patients under 65.
Why the study?
Sacubitril/Valsartan tolerability and clinical outcomes across age groups, especially in the elderly, remain unclear in HFrEF.
Does achieving tolerability of sacubitril/valsartan (≥50% target dose) improve clinical outcomes in Asian HFrEF patients across different age groups?
Cohort (n=1,987)
Yes
Does achieving tolerability of sacubitril/valsartan (≥50% target dose) improve clinical outcomes in Asian HFrEF patients across different age groups?
Achieving at least 50% of the target dose of sacubitril/valsartan significantly improves clinical outcomes in HFrEF patients across all age groups, though the magnitude of benefit is greater in younger patients.
Tolerability may lower event rates in younger Asian HFrEF patients; leaves open causal benefit pending randomized confirmation.
Background Sacubitril/Valsartan (S/V) benefits patients with heart failure with reduced ejection fraction (HFrEF), but its tolerability and clinical outcomes across age groups, especially the elderly, remain unclear. This real-world study evaluates these factors in an Asian cohort. Methods This retrospective cohort study analyzed data from the Treatment with Angiotensin Receptor Neprilysin Inhibitor for Taiwan Heart Failure Patients (TAROT-HF) registry (2017–2018). Patients were stratified into three age groups: <65, 65–74, and ≥75 years. Tolerability was defined as achieving at least 50% of the target S/V dosage (200 mg/day). Baseline characteristics, treatment doses, and clinical outcomes—including the composite of first unplanned heart failure hospitalization (HFH) or cardiovascular (CV) death, all-cause mortality, CV death, and HFH—were assessed over 5 years. Results Among 1,987 patients, older adults had more comorbidities and received lower S/V doses. Achieving tolerability significantly reduced composite outcome risk in patients <65 (HR = 0.40, 95% CI: 0.27–0.59, p < 0.001), all-cause mortality (HR = 0.30, p < 0.001), CV death (HR = 0.41, 95% CI: 0.21–0.80, p = 0.009), and HFH (HR = 0.41, 95% CI: 0.27–0.62, p < 0.001). Those aged 65–74 had similar benefits except for CV death. In patients ≥75, reaching tolerability improved composite outcome (HR = 0.60, 95% CI: 0.39–0.91, p = 0.017) and HFH (HR = 0.60, 95% CI: 0.38–0.95, p = 0.029). Partial dosing still provided protection in younger patients. Conclusion S/V improves HFrEF clinical outcomes across age groups in an Asian population, especially when achieving tolerability, defined as reaching ≥50% of the target dose. While this association was less pronounced in older patients, our result suggested that individualized dosing strategies should prioritize persistence in younger patients while accommodating tolerability in older populations.
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Chan et al. (2025) conducted a cohort in Heart failure with reduced ejection fraction (HFrEF) (n=1,987). Sacubitril/Valsartan vs. Discontinuation of Sacubitril/Valsartan was evaluated on Composite of first unplanned heart failure hospitalization or cardiovascular death (HR 0.40, 95% CI 0.27-0.59, p=<0.001). Achieving tolerability of sacubitril/valsartan (≥50% of target dose) reduced the composite risk of cardiovascular death or heart failure hospitalization by 60% (HR 0.40) in patients under 65.
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