NT-proBNP Response to Sacubitril/Valsartan in Hospitalized Heart Failure Patients With Reduced Ejection Fraction: TRANSITION Study

JACC Heart Fail. 2020 Oct;8(10):822-833. doi: 10.1016/j.jchf.2020.05.012. Epub 2020 Aug 12.


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).

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aftercare
  • Aminobutyrates* / pharmacology
  • Angiotensin Receptor Antagonists* / pharmacology
  • Biphenyl Compounds* / pharmacology
  • Drug Combinations
  • Heart Failure* / drug therapy
  • Humans
  • Natriuretic Peptide, Brain*
  • Patient Discharge
  • Peptide Fragments
  • Stroke Volume
  • Valsartan* / pharmacology


  • Aminobutyrates
  • Angiotensin Receptor Antagonists
  • Biphenyl Compounds
  • Drug Combinations
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Valsartan
  • sacubitril and valsartan sodium hydrate drug combination

Associated data

  • ClinicalTrials.gov/NCT02661217