Why the study?
Sacubitril/valsartan improves outcomes in patients with HFrEF, but age differences in its effects on biomarkers, KCCQ-23 scores, and cardiac remodeling remained to be explored.
Does sacubitril/valsartan improve biomarkers, cardiac remodeling, and health status similarly across different age groups in patients with HFrEF?
Does sacubitril/valsartan improve biomarkers, cardiac remodeling, and health status similarly across different age groups in patients with HFrEF?
Sacubitril/valsartan provides significant reverse cardiac remodeling and biomarker improvements across all age groups in HFrEF, though older patients may experience slightly attenuated NT-proBNP reductions and quality of life gains.
Answers are grounded in this paper and cite their sources.
Similar remodeling and safety across ages support Sac/Val in older HFrEF; leaves open whether attenuated NT-proBNP/KCCQ responses affect outcomes.
BACKGROUND: Sacubitril/valsartan (Sac/Val) improves outcomes in patients with heart failure with reduced ejection fraction (HFrEF). OBJECTIVES: In this study, the authors sought to explore age differences in effects of Sac/Val on biomarkers, Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 scores and cardiac remodeling. METHODS: After initiation and titration of Sac/Val, concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-cTnT), and soluble suppressor of tumorigenicity 2 (sST2) were measured and KCCQ-23 scores obtained from baseline to 12 months. Left ventricular ejection fraction (LVEF), and indexed left ventricular end-systolic (LVESVi) and indexed left ventricular end-diastolic (LVEDVi) and left atrial volume index (LAVi) volumes were measured with the use of echocardiography. Safety end points were assessed. Age-stratified analysis was performed for groups aged <65, 65-74, and ≥75 years. RESULTS: Among 794 participants with HFrEF (mean age 65.1 years, 28.5% women), compared with patients aged <65 years (n = 369), 65-74 years (n = 237), and those aged ≥75 years (n = 188), had similar reductions in hs-cTnT and sST2, but less NT-proBNP reduction (-45.6% vs -40.2% vs -30.5%, respectively; P = 0.02). Gains in KCCQ-23 were smaller (+11.8 vs +11.4 vs +6.0 points; P = 0.03) in patients aged ≥75 years, although similar proportions of each age group achieved ≥10-point and ≥20-point increases in KCCQ-23 by month 12. Improvements in LVEF, LVEDVi, LVESVi, and LAVi were similar among age groups. Incidence of safety end points was also similar. CONCLUSIONS: Sac/Val resulted in significant improvements in prognostic biomarkers and measures of cardiac remodeling and health status from baseline to month 12 across age categories. Older study participants showed somewhat blunted reduction in NT-proBNP and less improvement in KCCQ-23 overall summary scores. (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling, and Outcomes [PROVE-HF]; NCT02887183).
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Murphy et al. (2022) studied this question.
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