Practical guidance on the use of sacubitril/valsartan for heart failure

Heart Fail Rev. 2019 Mar;24(2):167-176. doi: 10.1007/s10741-018-9757-1.


Sacubitril/valsartan is a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI) that has been recommended in clinical practice guidelines to reduce morbidity and mortality in patients with chronic, symptomatic heart failure (HF) with reduced ejection fraction (HFrEF). This review provides an overview of ARNI therapy, proposes strategies to improve the implementation of sacubitril/valsartan in clinical practice, and provides clinicians with evidence-based, practical guidance on the use of sacubitril/valsartan in patients with HFrEF. Despite evidence demonstrating the benefits of ARNI therapy over standard of care, only a fraction of eligible patients takes sacubitril/valsartan. Barriers preventing the prescription of sacubitril/valsartan in eligible patients may include practitioners' unfamiliarity with ARNIs, safety concerns, and payer reimbursement issues. The optimal implementation of sacubitril/valsartan in clinical practice has the potential to reduce the overall burden of HF. Throughout this review, we describe our experience with sacubitril/valsartan, including strategies for the management of adverse events and common patient concerns. In addition, a strategy for the gradual introduction of sacubitril/valsartan using a treatment sequence scheme is proposed.

Keywords: Angiotensin receptor-neprilysin inhibitor; Cardiovascular; Heart failure; Reduced ejection fraction; Sacubitril/valsartan.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aminobutyrates / adverse effects
  • Aminobutyrates / therapeutic use*
  • Angiotensin Receptor Antagonists / adverse effects
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Biphenyl Compounds
  • Comorbidity
  • Cost of Illness
  • Drug Combinations
  • Evidence-Based Medicine
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Heart Failure / physiopathology
  • Humans
  • Middle Aged
  • Morbidity / trends
  • Mortality / trends
  • Practice Guidelines as Topic
  • Stroke Volume / drug effects
  • Tetrazoles / adverse effects
  • Tetrazoles / therapeutic use*
  • Treatment Outcome
  • Valsartan
  • Ventricular Dysfunction, Left / physiopathology


  • Aminobutyrates
  • Angiotensin Receptor Antagonists
  • Biphenyl Compounds
  • Drug Combinations
  • Tetrazoles
  • Valsartan
  • sacubitril and valsartan sodium hydrate drug combination