sacubutril

Last edited 01/2021 and last reviewed 05/2023

Sacubitril/valsartan (S/V) is an angiotensin receptor blocker/neprilysin inhibitor (ARNI) and has been shown to improve mortality and HF hospitalization inpatients with HF with reduced ejection fraction (HFrEF) (1,2)

Sacubitril and cardiac remodeling:

• in PROVE-HF (ProspectiveStudy of Biomarkers, Symptom Improvement and Ventricular Remodeling During Entres to Therapy for Heart Failure;NCT02887183) study (3) demonstrated that S/V had favorable effects on measures of cardiac reverse remodeling
• including increase in left ventricular (LV) ejection fraction (LVEF) over a 12-month period, as well as simultaneous improvements inother measures such as left atrial (LA) volume index(LAVI)
• changes in measures of cardiac reverse remodeling were shown to strongly associate with reductions in N-terminal pro-B type natriuretic peptide (NT-proBNP) concentrations; because it is an inert fragment, NT-proBNP is only a marker of HF, not a mediator
  
  
• a prespecified substudy of PROVE-HF showed a rapid significant rise in atrial natriuretic peptide (ANP) was associated with greater improvements in LVEF and reduction of LAVI, measures of cardiac remodeling (4)
  • the study results suggest a role of ANP as a mechanism of benefit by sacubitril/valsartan

Reference:

• Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Eur Heart J 2016;37:2129-200.
• Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/ AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart FailureSociety of America. J Am Coll Cardiol 2017;70: 776-803
• Januzzi JL Jr., Prescott MF, Butler J, et al. Association of change in N-terminal pro-B-type natriuretic peptide following initiation of sacubitril-valsartan treatment with cardiac structure and function in patients with heart failure with reduced ejection fraction. JAMA 2019;322:1-11.
• Murphy SP, Prescott MF, Camachoet A et al.Early increase ANP after ARNI initiation associated with reverse cardiac remodeling in HFrEF JACC Heart Fail. 2020, doi.org/10.1016/j.jchf.2020.09.013