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Angiotensin receptor neprilysin inhibition (ARNI)

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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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


  • 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,

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