From the Guidelines
Entresto (sacubitril/valsartan) is recommended for the treatment of heart failure with reduced ejection fraction (HFrEF) in adults with chronic symptomatic heart failure (NYHA Class II-IV) to reduce the risk of cardiovascular death and hospitalization, as stated in the 2024 ESC guidelines for the management of chronic coronary syndromes 1. The medication can replace ACE inhibitors or ARBs in patients who remain symptomatic despite optimal medical therapy. Some key points to consider when prescribing Entresto include:
- The typical starting dose is 24/26 mg twice daily, which can be titrated to a target dose of 97/103 mg twice daily as tolerated.
- Before initiating Entresto, ACE inhibitors should be discontinued at least 36 hours prior to avoid angioedema risk.
- Entresto works through a dual mechanism: valsartan blocks angiotensin II receptors while sacubitril inhibits neprilysin, preventing the breakdown of beneficial natriuretic peptides.
- Patients should be monitored for hypotension, kidney function changes, hyperkalemia, and angioedema during treatment. It is also important to note that Entresto is recommended as a replacement for an ACE-I or ARB in CCS patients with HFrEF to reduce the risk of HF hospitalization and death, as stated in the 2024 ESC guidelines for the management of chronic coronary syndromes 1. Additionally, the 2022 AHA/ACC/HFSA guideline for the management of heart failure also supports the use of Entresto in patients with HFrEF 1. However, the most recent and highest quality study, the 2024 ESC guidelines for the management of chronic coronary syndromes 1, should be prioritized when making a definitive recommendation.
From the FDA Drug Label
Sacubitril and valsartan tablets are 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 and reduced ejection fraction. (1. 1) for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older. Sacubitril and valsartan tablets reduces NT-proBNP and is expected to improve cardiovascular outcomes. (1. 2)
The indications for Entresto (sacubitril and valsartan tablets) in heart failure are:
- Reduction of risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure and reduced ejection fraction.
- Treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older. 2
From the Research
Indications for Entresto in Heart Failure
- Entresto (sacubitril/valsartan) is indicated for the treatment of heart failure with reduced ejection fraction (HFrEF) 3, 4, 5.
- The drug has been shown to reduce the incidence of death from cardiovascular causes or first hospitalization for worsening heart failure in patients with HFrEF 3, 4, 5.
- Entresto is also being considered as a possible treatment option for heart failure with preserved ejection fraction (HFpEF) 6.
- The efficacy and safety of sacubitril/valsartan have been demonstrated in various studies, including the PARADIGM-HF trial, which showed that the drug reduced the risk of cardiovascular death or HF hospitalization compared to enalapril 3, 5, 7.
- The benefits of sacubitril/valsartan have been observed in different subpopulations, including patients with advanced chronic kidney disease, hypotension, and those with type 2 diabetes mellitus 4, 5.
- The drug has been shown to be safe and well-tolerated, with a similar risk reduction in both women and men with HFrEF 7.