Novel doses of sacubitril/valsartan in patients unable to tolerate traditional therapy: Effects on N-terminal pro B-type natriuretic peptide levels

Clin Cardiol. 2021 Jan;44(1):85-90. doi: 10.1002/clc.23509. Epub 2020 Dec 5.


Background: Widespread use of angiotensin receptor blocker and neprilysin inhibitor (ARNI) remains low, and many patients are unable to tolerate the medication due to hypotension at the currently recommended starting dose.

Hypothesis: The aim of this study is to assess if lower than standard doses of ARNI, sacubitril/valsartan (S/V), significantly reduces NT-proBNP and leads to any change in diuretic dose, serum potassium, or creatinine.

Methods: In a retrospective study of 278 patients who were started on a low dose S/V at a single medical center, 45 patients were selected for the study cohort. Patients were subcategorized to Group 1 (n = 10): very low dose S/V (half a tab of 24/26 mg BID), Group 2 (n = 10): very low dose titrated to low dose S/V, and Group 3 (n = 25): low dose S/V (24/26 mg BID). NT-proBNP, diuretic dose, serum potassium, and creatinine were compared before and after initiation of S/V.

Results: Among all groups, there was a significant reduction in NT-proBNP level (Group 1: p < .01, Group 2: p < .01, and Group 3: p < .001). In addition, there was a significant reduction in diuretic dose across all groups combined (furosemide 53 mg/day vs. 73 mg/day; p = .03), with 17.8% (8/45) patients being able to discontinue their diuretic completely. There was no significant change in potassium or creatinine.

Conclusions: Lower than standard dose of S/V significantly reduces NT-proBNP and diuretic requirement without change in potassium or creatinine, which provides hope that patients who cannot tolerate standard doses of S/V due to hypotension may be able to receive the benefits of S/V therapy.

Keywords: N-terminal pro brain natriuretic peptide; angiotensin receptor blocker and neprilysin inhibitor; heart failure with reduced ejection fraction; loop diuretics.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Aminobutyrates / therapeutic use*
  • Angiotensin Receptor Antagonists / therapeutic use
  • Biomarkers / blood
  • Biphenyl Compounds / therapeutic use*
  • Drug Combinations
  • Drug Tolerance*
  • Female
  • Heart Failure / blood
  • Heart Failure / drug therapy*
  • Humans
  • Male
  • Natriuretic Peptide, Brain / blood*
  • Retrospective Studies
  • Valsartan / therapeutic use*


  • Aminobutyrates
  • Angiotensin Receptor Antagonists
  • Biomarkers
  • Biphenyl Compounds
  • Drug Combinations
  • Natriuretic Peptide, Brain
  • Valsartan
  • sacubitril and valsartan sodium hydrate drug combination