What are the benefits of Entresto (sacubitril/valsartan)?

From the Guidelines

Entresto (sacubitril/valsartan) is recommended for patients with heart failure with reduced ejection fraction (HFrEF) to reduce the risk of cardiovascular death and hospitalization by about 20% compared to standard ACE inhibitor therapy, as shown in the PARADIGM-HF trial 1. The medication combines an angiotensin receptor blocker (valsartan) with a neprilysin inhibitor (sacubitril) to provide dual action in managing heart failure.

Benefits of Entresto

• Reduces the risk of cardiovascular death and hospitalization for heart failure
• Improves quality of life with reduced symptoms like shortness of breath, fatigue, and swelling
• Works by relaxing blood vessels and reducing sodium retention, which decreases the workload on the heart

Dosage and Administration

• Usually started at a lower dose (24/26 mg or 49/51 mg twice daily) and may be titrated up to 97/103 mg twice daily as tolerated
• Should not be taken with ACE inhibitors, and patients should wait 36 hours after stopping an ACE inhibitor before starting Entresto to avoid the risk of angioedema, as recommended by the 2017 ACC/AHA/HFSA focused update 1

Monitoring and Side Effects

• Patients should have their blood pressure, kidney function, and potassium levels monitored regularly while taking Entresto
• Common side effects include low blood pressure, increased potassium levels, and kidney problems

Clinical Guidelines

• The 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure recommend sacubitril/valsartan as a replacement for an ACE inhibitor to further reduce the risk of HF hospitalization and death in ambulatory patients with HFrEF who remain symptomatic despite optimal treatment with an ACE inhibitor, a beta-blocker, and an MRA 1
• The 2017 ACC/AHA/HFSA focused update recommends ARNI therapy, such as sacubitril/valsartan, for patients with chronic symptomatic HFrEF NYHA class II or III who tolerate an ACE inhibitor or ARB, to further reduce morbidity and mortality 1

From the FDA Drug Label

Sacubitril and valsartan tablets are 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. Sacubitril and valsartan tablet is indicated 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 reduces NT-proBNP and is expected to improve cardiovascular outcomes.

The benefits of Entresto (sacubitril/valsartan) include:

• Reducing 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 2
• Treating symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older, with expected improvement in cardiovascular outcomes due to reduction in NT-proBNP 2

From the Research

Benefits of Entresto (Sacubitril/Valsartan)

The benefits of Entresto (sacubitril/valsartan) include:

• Reduced incidence of death from cardiovascular causes or first hospitalization for worsening heart failure 3
• Superiority to enalapril in reducing death from any cause and limiting the progression of heart failure 3
• Improved cardiovascular outcomes compared to angiotensin-converting enzyme (ACE) inhibitor therapy 4
• Reduced 5-year all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF) and coexisting end-stage renal disease (ESRD) 5
• Greater left ventricular ejection fraction (LVEF) improvement in HFrEF patients with coexisting ESRD compared to candesartan or valsartan 5
• Reduced rates of cardiovascular death and HF hospitalization, as well as all-cause mortality, across the full spectrum of LVEF 6
• Clinical efficacy in blood pressure reduction in hypertensive patients with and without HFpEF, and a reduction in hospitalizations and mortality for patients with HFrEF 7

Therapeutic Effects

The therapeutic effects of sacubitril/valsartan include:

• Inhibition of angiotensin receptor and neprilysin, modulating the renin-angiotensin-aldosterone system and vasoactive substances such as natriuretic peptides 4
• Increase in endogenous natriuretic peptides while inhibiting the renin-angiotensin-aldosterone system 7
• Variation in treatment benefits by LVEF, with benefits appearing to extend to patients with heart failure and mildly reduced ejection fraction, particularly in women 6

Clinical Outcomes

The clinical outcomes of sacubitril/valsartan include:

• Reduced hospitalization and risk of cardiovascular death for patients with HFrEF in New York Heart Association (NYHA) functional class II-IV 7
• Similar rates of noncardiovascular death among patients in the highest versus the lowest groups of LVEF 6
• Lower incidence rates of cardiovascular death and HF hospitalization among patients in the highest versus the lowest groups of LVEF 6