Elsevier

JACC: Heart Failure

Volume 8, Issue 10, October 2020, Pages 822-833
JACC: Heart Failure

Focus Issue: Angiotensin-Neprilysin Inhibition: Novel Insights
Clinical Research
NT-proBNP Response to Sacubitril/Valsartan in Hospitalized Heart Failure Patients With Reduced Ejection Fraction: TRANSITION Study

https://doi.org/10.1016/j.jchf.2020.05.012Get rights and content
Under a Creative Commons license
open access

Abstract

Objectives

This study examined the effects of sacubitril/valsartan on N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels and determined patient characteristics associated with favorable NT-proBNP reduction response.

Background

NT-proBNP levels reflect cardiac wall stress and predict event risk in patients with acute decompensated heart failure (ADHF).

Methods

Post-hoc analysis of the TRANSITION (Comparison of Pre- and Post-discharge Initiation of Sacubitril/Valsartan Therapy in HFrEF Patients After an Acute Decompensation Event) study, including stabilized ADHF patients with reduced ejection fraction, randomized to open-label sacubitril/valsartan initiation in-hospital (pre-discharge) versus post-discharge. NT-proBNP was measured at randomization (baseline), discharge, and 4 and 10 weeks post-randomization. A favorable NT-proBNP response was defined as reduction to ≤1,000 pg/ml or >30% from baseline.

Results

In patients receiving sacubitril/valsartan in-hospital, NT-proBNP was reduced by 28% at discharge, with 46% of patients obtaining favorable NT-proBNP reduction response compared with a 4% reduction and 18% favorable response rate in patients initiated post-discharge (p < 0.001). NT-proBNP was reduced similarly in patients initiating sacubitril/valsartan pre- and post-discharge (reduction at 4 weeks: 25%/22%; 10 weeks: 38%/34%) with comparable favorable response rates (46%/42% and 51%/48% at 4 and 10 weeks, respectively). NT-proBNP favorable response at 4 weeks was associated with lower risk of first heart failure (HF) rehospitalization or cardiovascular death through 26 weeks (hazard ratio: 0.57; 95% confidence interval [CI]: 0.38 to 0.86; p = 0.007). Predictors of a favorable response at 4 weeks were starting dose ≥49/51 mg twice daily, higher baseline NT-proBNP, lower baseline serum creatinine, de novo HF, no atrial fibrillation, angiotensin-converting enzyme inhibitor–naive or angiotensin receptor blocker–naive, and no prior myocardial infarction.

Conclusions

In-hospital initiation of sacubitril/valsartan produced rapid reductions in NT-proBNP, statistically significant at discharge. A favorable NT-proBNP response over time was associated with a better prognosis and predicted by higher starting dose and predisposing clinical profile. (Comparison of Pre- and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event [TRANSITION]; NCT02661217)

Key Words

acute decompensated heart failure
heart failure with reduced ejection fraction
N-terminal pro–B-type natriuretic peptide
sacubitril/valsartan
TRANSITION study

Abbreviations and Acronyms

ACE
angiotensin-converting enzyme
ADHF
acute decompensated heart failure
AF
atrial fibrillation
ARB
angiotensin receptor blocker
CI
confidence interval
CV
cardiovascular
HF
heart failure
HFrEF
heart failure with reduced ejection fraction
HR
hazard ratio
NT-proBNP
N-terminal pro–B-type natriuretic peptide

Cited by (0)

This study was funded by Novartis Pharma AG, Basel, Switzerland. Dr. Pascual-Figal has served on the advisory board for and/or received speaker honoraria from Novartis, Servier, Roche, AstraZeneca, Vifor, Pfizer, and Abbott. Dr. Wachter has served on the advisory board for and/or received speaker honoraria from Boehringer Ingelheim, Bayer, CVRx, Medtronic, Novartis, Pfizer, Sanofi, and Servier; and received research grant supports from Boehringer Ingelheim, the European Union, and Bundesministerium für Bildung und Forschung. Dr. Senni has received consultancy fees and/or speaker honoraria from Novartis, Bayer, Abbott, Merck, AstraZeneca, Vifor Pharma, and Boehringer Ingelheim. Drs. Bao, Noè, Schwende, Butylin, and Prescott are employees of Novartis.

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 JACC: Heart Failure author instructions page.