What is the use of Entresto (sacubitril/valsartan)?

From the Guidelines

Entresto (sacubitril/valsartan) is recommended as a replacement for an ACE inhibitor to further reduce the risk of heart failure hospitalization and death in ambulatory patients with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal treatment with an ACE inhibitor, a beta-blocker, and a mineralocorticoid receptor antagonist (MRA) 1. The use of Entresto is based on its ability to enhance the body's protective neurohormonal systems while inhibiting the harmful effects of the renin-angiotensin-aldosterone system, which helps reduce strain on the heart, improve blood flow, and decrease fluid retention. Some key points to consider when using Entresto include:

• The typical starting dose is 24/26 mg taken twice daily, which may be increased to a target dose of 97/103 mg twice daily as tolerated 1.
• Patients should take Entresto with or without food, swallowing the tablets whole.
• It's essential to monitor blood pressure regularly while taking this medication, as it can cause hypotension.
• Patients should also be aware of potential side effects, including dizziness, cough, and elevated blood potassium levels.
• Before starting Entresto, patients should inform their doctor about all other medications they're taking, especially ACE inhibitors, as these must be discontinued at least 36 hours before beginning Entresto to avoid potentially serious interactions 1.
• Pregnant women should not take Entresto due to risks of fetal harm. Regular follow-ups with a healthcare provider are necessary to assess the medication's effectiveness and adjust the dose if needed. Patients should continue taking Entresto as prescribed, even if they feel better, to maintain its beneficial effects on heart function. In patients with borderline blood pressure, careful administration and follow-up are advised, and empiric modest lowering of loop diuretic agents has been found to mitigate the hypotensive effects of sacubitril/valsartan 1. The role of sacubitril/valsartan in more advanced forms of HFrEF continues to be explored, and it remains indicated in patients with NYHA class IV symptoms 1.

From the FDA Drug Label

Sacubitril and valsartan tablet is a combination of sacubitril, a neprilisin inhibitor, and valsartan, an angiotensin II receptor blocker, and is indicated: • to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal. • for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older. Sacubitril and valsartan tablet reduce NT-proBNP and is expected to improve cardiovascular outcomes.

The use of Entresto (sacubitril/valsartan) is to:

• Reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure, particularly those with left ventricular ejection fraction (LVEF) below normal.
• Treat symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older. 2

From the Research

Use of Entresto (Sacubitril/Valsartan)

The use of Entresto (sacubitril/valsartan) is primarily for the treatment of chronic heart failure with reduced ejection fraction (HFrEF) [ 3 ]. Key points about its use include:

• Sacubitril/valsartan is an orally administered supramolecular sodium salt complex of the neprilysin inhibitor prodrug sacubitril and the angiotensin receptor blocker (ARB) valsartan [ 3 ].
• It was approved in the US and the EU for the treatment of chronic heart failure (NYHA class II-IV) with reduced ejection fraction (HFrEF) [ 3 ].
• The large, randomized, double-blind, PARADIGM-HF trial showed that sacubitril/valsartan reduced the incidence of death from cardiovascular causes or first hospitalization for worsening heart failure significantly more than the angiotensin converting enzyme (ACE) inhibitor enalapril [ 3 ].

Indications and Eligibility

Indications and eligibility for sacubitril/valsartan treatment include:

• International guidelines recommend the introduction of sacubitril/valsartan in patients with heart failure (HF) and reduced ejection fraction (EF), who remain symptomatic, despite optimal uptitrated therapy [ 4 ].
• In patients with HF and reduced EF on optimized guideline-directed medical therapy (GDMT), indication to sacubitril/valsartan treatment is around 38% [ 4 ].
• Sacubitril/valsartan is a more effective replacement for an ACE inhibitor or an ARB in the treatment of HFrEF [ 3 ].

Benefits and Safety

Benefits and safety of sacubitril/valsartan include:

• Sacubitril/valsartan has a beneficial effect in patients with HFrEF, with a reduction in all-cause mortality and serious adverse events [ 5 ].
• The effects of sacubitril/valsartan have been assessed in a systematic review, which showed evidence of a beneficial effect in HFrEF participants [ 5 ].
• Sacubitril/valsartan was generally well tolerated, with no increase in life-threatening adverse events, but with increased occurrences of hypotension and nonserious angioedema [ 3 ].

Clinical Guidance

Clinical guidance on the use of sacubitril/valsartan includes:

• Sacubitril/valsartan is recommended in clinical practice guidelines to reduce morbidity and mortality in patients with chronic, symptomatic heart failure (HF) with reduced ejection fraction (HFrEF) [ 6 ].
• Practical guidance on the use of sacubitril/valsartan in patients with HFrEF includes strategies to improve the implementation of sacubitril/valsartan in clinical practice and evidence-based guidance on the use of sacubitril/valsartan [ 6 ].