Elsevier

JACC: Heart Failure

Volume 10, Issue 12, December 2022, Pages 976-988
JACC: Heart Failure

Clinical Research
Age Differences in Effects of Sacubitril/Valsartan on Cardiac Remodeling, Biomarkers, and Health Status

https://doi.org/10.1016/j.jchf.2022.07.001Get rights and content
Under a Creative Commons license
open access

Abstract

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)

Key Words

biomarkers
cardiac remodeling
heart failure
sacubitril/valsartan

Abbreviations and Acronyms

ACEI
angiotensin-converting enzyme inhibitor
ARB
angiotensin receptor blocker
ARNI
angiotensin receptor–neprilysin inhibitor
GDMT
guideline-directed medical therapy
hs-cTnT
high-sensitivity cardiac troponin T
KCCQ-23
Kansas City Cardiomyopathy Questionnaire-23
LAVi
left atrial volume index
LVEDVi
left ventricular end-diastolic volume index
LVEF
left ventricular ejection fraction
LVESVi
left ventricular end-systolic volume index
NT-proBNP
N-terminal pro–B-type natriuretic peptide
Sac/Val
sacubitril/valsartan
sST2
soluble suppressor of tumorigenicity 2

Cited by (0)

Barry Greenberg, MD, served as Guest Editor-in-Chief for this paper.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.