What is the indication for using Entresto (sacubitril/valsartan)?

From the Guidelines

Entresto (sacubitril/valsartan) is indicated for the treatment of heart failure with reduced ejection fraction (HFrEF) in adults with chronic heart failure (NYHA Class II-IV) who have an ejection fraction of 40% or less to reduce the risk of cardiovascular death and hospitalization. The recommendation to use Entresto in patients with HFrEF is based on the results of the PARADIGM-HF trial, which demonstrated a significant reduction in hospitalizations and mortality with sacubitril-valsartan compared to enalapril 1.

Key Considerations for Entresto Use

• Entresto should be started at a dose of 49/51 mg (sacubitril/valsartan) twice daily, though patients not currently taking an ACE inhibitor or ARB, or those on low doses, may start at 24/26 mg twice daily.
• Before starting Entresto, ACE inhibitors must be discontinued at least 36 hours prior to avoid the risk of angioedema, as supported by guidelines 1.
• Entresto works through a dual mechanism of action: sacubitril inhibits neprilysin, increasing levels of peptides that counter the neurohormonal overactivation harmful in heart failure, while valsartan blocks angiotensin II receptors, reducing vasoconstriction and sodium retention.
• Patients with a history of angioedema related to previous ACE inhibitor or ARB therapy should not be started on Entresto due to the risk of recurrence 1.

Clinical Evidence Supporting Entresto Use

• The PARADIGM-HF trial demonstrated that sacubitril-valsartan significantly reduced the risk of cardiovascular death and hospitalization for heart failure compared to enalapril in patients with HFrEF 1.
• A cost-effectiveness analysis of the PARADIGM-HF trial results found that sacubitril-valsartan provided high value compared to enalapril, with costs per quality-adjusted life year (QALY) less than $60,000 1.
• Guidelines recommend that patients with chronic stable HFrEF who tolerate ACE inhibitors and ARBs should be switched to ARNi, such as sacubitril-valsartan, to further reduce morbidity and mortality 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 and reduced ejection fraction. for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older.

The indication for using Entresto (sacubitril/valsartan) is:

• to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure and reduced ejection fraction.
• for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older. 2

From the Research

Indication for Using Entresto (Sacubitril/Valsartan)

The indication for using Entresto (sacubitril/valsartan) is primarily for the treatment of heart failure with reduced ejection fraction (HFrEF) 3, 4, 5, 6, 7.

• Heart failure with reduced ejection fraction (HFrEF) is a condition where the heart is unable to pump enough blood to meet the body's needs, resulting in symptoms such as shortness of breath, fatigue, and swelling 4, 5, 6.
• Entresto is an angiotensin receptor neprilysin inhibitor, which works by blocking the action of angiotensin II, a potent vasoconstrictor, and increasing the levels of natriuretic peptides, which help to relax and dilate blood vessels 4, 6.
• The use of Entresto has been shown to reduce the risk of cardiovascular death and hospitalization for heart failure by 20% compared to enalapril, a commonly used ACE inhibitor 6.
• Entresto is indicated for patients with HFrEF who remain symptomatic despite optimal medical therapy, including ACE inhibitors or angiotensin receptor blockers (ARBs) 7.
• The eligibility for sacubitril/valsartan treatment in real-life patients with chronic systolic heart failure has been found to be around 38% in patients who are symptomatic (NYHA ≥2) and have reduced ejection fraction despite optimized guideline-directed medical therapy (GDMT) 7.

Patient Selection

The selection of patients for Entresto treatment should be based on the following criteria:

• Patients with HFrEF who remain symptomatic despite optimal medical therapy, including ACE inhibitors or ARBs 7.
• Patients with a reduced ejection fraction (EF ≤40%) 5, 6.
• Patients who are able to tolerate the medication and do not have any contraindications, such as a history of angioedema or hypotension 6.

Clinical Evidence

The clinical evidence supporting the use of Entresto in HFrEF patients includes:

• The PARADIGM-HF trial, which demonstrated a 20% reduction in cardiovascular death and hospitalization for heart failure compared to enalapril 6.
• Real-life studies, which have shown that Entresto is effective in reducing symptoms and improving quality of life in patients with HFrEF 7.
• Studies that have demonstrated the efficacy of Entresto in patients with HFrEF regardless of disease duration 5.