From the Guidelines
Entresto is recommended as a replacement for an ACE inhibitor or ARB in patients with heart failure with reduced ejection fraction (HFrEF) to reduce the risk of heart failure hospitalization and death, as supported by the 2024 ESC guidelines for the management of chronic coronary syndromes 1. The typical starting dose of Entresto is 24/26 mg twice daily, which can be increased to 49/51 mg and then 97/103 mg twice daily as tolerated, according to the 2021 update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment 1. Some key points to consider when prescribing Entresto include:
- Discontinuing any ACE inhibitors at least 36 hours before starting Entresto to avoid angioedema risk, as recommended by the 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure 1.
- Monitoring blood pressure, kidney function, and potassium levels regularly, as these can be affected by Entresto, as noted in the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.
- Being aware of potential side effects, including hypotension, hyperkalemia, cough, dizziness, and renal impairment, as reported in the 2019 ACC/AHA versus ESC guidelines on heart failure 1. Entresto works by simultaneously blocking harmful neurohormonal systems while enhancing beneficial pathways, leading to reduced cardiac workload, improved cardiac output, and decreased fluid retention, as described in the 2021 update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment 1. This dual mechanism provides superior outcomes compared to ACE inhibitors alone in heart failure management, as supported by the 2024 ESC guidelines for the management of chronic coronary syndromes 1.
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. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal. (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 main indications for Entresto (sacubitril/valsartan) are:
- To reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure.
- For the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older. Entresto is expected to improve cardiovascular outcomes by reducing NT-proBNP 2.
From the Research
Entresto Overview
- Entresto, also known as sacubitril/valsartan, is a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI) 3, 4
- It combines a neprilysin inhibitor with an angiotensin receptor blocker, increasing levels of circulating natriuretic peptides and resulting in natriuretic, diuretic, and vasodilatory effects 3
Clinical Outcomes
- The PARADIGM-HF trial demonstrated that sacubitril/valsartan significantly reduced the primary endpoint of cardiovascular mortality and heart failure hospitalization, compared with enalapril 3
- A retrospective, observational study found that sacubitril-valsartan use was associated with lower 12-month morbidity and mortality in patients with heart failure and ejection fraction up to 60% 5
- A comparative effectiveness study found that sacubitril-valsartan was associated with lower risks of death and hospitalization compared with ACE/ARB therapy in heart failure with reduced ejection fraction 6
Potential Uses
- Sacubitril/valsartan has been recommended in clinical practice guidelines to reduce morbidity and mortality in patients with chronic, symptomatic heart failure with reduced ejection fraction (HFrEF) 4
- It may also be effective in treating hypertension, particularly in elderly patients with age-related hypertension phenotypes 7
Safety and Tolerability
- Initiating the lower dosage form of sacubitril/valsartan is warranted in patients with severe renal impairment, moderate hepatic impairment, and low blood pressure, and close monitoring is warranted in such patients 3
- A 36-hour washout period is recommended when switching patients from an angiotensin-converting enzyme inhibitor to sacubitril/valsartan 3