Early B-Type Natriuretic Peptide Change in HFrEF Patients Treated With Sacubitril/Valsartan: A Pooled Analysis of EVALUATE-HF and PROVE-HF

• Main Authors: Claggett, B. (Author), Desai, A.S (Author), Fang, J.C (Author), Januzzi, J.L (Author), Mitchell, G.F (Author), Murphy, S.P (Author), Myhre, P.L (Author), Prescott, M.F (Author), Solomon, S.D (Author), Ward, J.H (Author)
• Format: Article
• Language: English
• Published: Elsevier Inc. 2022
• Subjects: adult; aged; amino terminal pro brain natriuretic peptide; ARNI; arterial stiffness; Article; biomarker; blood level; blood sampling; BNP; clinical outcome; cohort analysis; controlled study; cyclic GMP; female; heart failure with reduced ejection fraction; heart ventricle remodeling; HFrEF; human; major clinical study; male; middle aged; prescription; sacubitril plus valsartan; sacubitril/valsartan; therapy effect
• Online Access: View Fulltext in Publisher

 Objectives: This study assessed changes in B-type natriuretic peptide (BNP) among patients with heart failure with reduced ejection fraction (HFrEF) treated with sacubitril/valsartan (Sac/Val) according to standard prescribing information. Background: Through inhibition of neprilysin, Sac/Val may increase BNP concentrations. Methods: In an individual patient analysis from the EVALUATE-HF (Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction) (n = 221) and the PROVE-HF (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes) (n = 146) studies, we examined changes in BNP, N-terminal pro-BNP (NT-proBNP), and urinary cyclic guanosine monophosphate (ucGMP) from baseline to week 4 and week 12. Results: Median (IQRs) concentration of BNP at baseline, week 4, and week 12 were 145 [IQR: 55-329], 136 [IQR: 50-338], and 135 [IQR: 51-299] ng/L, respectively. There was no significant change from baseline to week 4 (0% [−30% to +41%]; P = 0.36) or week 12 (+1% [−36% to +50%]; P = 0.97). By week 12, one-half of the study participants had a BNP decline. There was no association between Sac/Val dose and BNP changes. Change in BNP was directly associated with change in NT-proBNP (rho: = 0.81; P < 0.001), which decreased by −30% (−50% to −8%) and −32% (−54% to −1%) to weeks 4 and 12 (P < 0.001 for both). In contrast, change in BNP was only weakly associated with change in ucGMP (rho: = 0.19; P < 0.001). Increases in ucGMP were observed regardless of whether BNP was decreased (+11% [−34% to +115%]), unchanged (+34% [−15% to +205%]), or increased (+57% [−12% to +14%]). Conclusions: In this pooled analysis of patients with HFrEF with standard indications for Sac/Val treatment, there was no significant overall increase in BNP concentrations, and patients demonstrated increase in ucGMP regardless of the trajectory of BNP change. (Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction [EVALUATE-HF]; NCT02874794) (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183). © 2022 The Authors