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

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. The typical starting dose is 24/26 mg twice daily, which can be increased to 49/51 mg and then 97/103 mg twice daily as tolerated 1. Patients should be monitored for hypotension, kidney function changes, and hyperkalemia. Entresto should not be taken with ACE inhibitors (wait 36 hours after stopping ACE inhibitors before starting Entresto) or by pregnant women. Common side effects include dizziness, low blood pressure, and cough. The medication has been shown to reduce hospitalizations and mortality in heart failure patients compared to traditional treatments, as demonstrated in the PARADIGM-HF trial 1. It works by inhibiting neprilysin (increasing beneficial peptides) while blocking angiotensin II receptors, providing dual action to improve heart function and reduce strain on the cardiovascular system.

Some key considerations for the use of Entresto include:

• Patients with a history of angioedema should not be administered Entresto due to the risk of recurrence 1.
• Entresto should not be administered concomitantly with ACE inhibitors or within 36 hours of the last dose of an ACE inhibitor 1.
• The medication has been shown to be high value in terms of cost-effectiveness, with costs per QALY less than $60,000 1.
• Clinicians should be advised that Entresto may exert a more noteworthy effect on blood pressure when compared with ACEIs/ARBs, and careful administration and follow-up are advised in patients with borderline blood pressure 1.

Overall, Entresto is a valuable treatment option for patients with HFrEF, and its use should be considered in accordance with current guidelines and clinical evidence.

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. Sacubitril and valsartan tablets are prescription medicine used to treat: • adults with long-lasting (chronic) heart failure to help reduce the risk of death and hospitalization. • certain children 1 year of age and older who have symptomatic heart failure

The drug Entresto is also known as sacubitril/valsartan. It is used to treat:

• Adults with chronic heart failure to reduce the risk of cardiovascular death and hospitalization.
• Children 1 year of age and older with symptomatic heart failure 2 2.

From the Research

Overview of Sacubitril/Valsartan

• Sacubitril/valsartan is a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI) that combines a neprilysin inhibitor with an angiotensin receptor blocker 3.
• This therapy increases levels of circulating natriuretic peptides, resulting in natriuretic, diuretic, and vasodilatory effects 3.

Clinical Use and Effectiveness

• Sacubitril/valsartan 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) 4.
• 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 meta-analysis of randomized trials found that sacubitril/valsartan reduced total mortality, cardiovascular mortality, and worsening heart failure when compared to sub-equivalent doses of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) 5.

Patient Selection and Dosing

• 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.
• Sacubitril/valsartan is contraindicated in patients receiving concomitant angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and those with a history of angioedema 3.

Potential Uses Beyond Heart Failure

• Sacubitril/valsartan has been developed for the management of hypertension, due to its unique anti-aging properties 6.
• The drug may be effective in suppressing the age-related continuum from hypertension to heart failure, and could be clinically useful not only for secondary prevention, but also as primary prevention of heart failure in uncontrolled elderly hypertensive patients 6.