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

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Last updated: February 13, 2025View editorial policy

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From the Guidelines

Entresto (sacubitril/valsartan) significantly reduces morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF).

Benefits of Entresto

  • Reduces the composite endpoint of cardiovascular death or HF hospitalization by 20% relative to enalapril, as shown in the PARADIGM-HF trial 1
  • Decreases hospitalizations and mortality in patients with mild-to-moderate HF who are able to tolerate both a target dose of enalapril and then subsequently an ARNi (sacubitril-valsartan) 1
  • Provides high value for patients with chronic HF, with costs per QALY <$60,000, according to multiple model-based analyses 1
  • Is recommended for patients with chronic HFrEF to reduce morbidity and mortality, in conjunction with evidence-based beta blockers and aldosterone antagonists in selected patients 1

Key Considerations

  • Entresto should not be administered concomitantly with ACE inhibitors or within 36 hours of the last dose of an ACE inhibitor, due to the risk of angioedema 1
  • Patients with a history of angioedema should not be administered Entresto, due to the concern of recurrence of angioedema 1
  • Entresto is associated with a higher incidence of hypotension and angioedema compared to enalapril, but has a comparable incidence of angioedema when compared to enalapril 1
  • The use of Entresto in patients with heart failure with preserved ejection fraction (HFpEF) is still being studied, with mixed results, as seen in the PARAGON-HF trial 1

From the FDA Drug Label

Sacubitril and Valsartan Tablets are a prescription medicine used to treat: adults with long-lasting (chronic) heart failure to help reduce the risk of death and hospitalization. Sacubitril and Valsartan Tablets works better when the heart cannot pump a normal amount of blood to the body. certain children 1 year of age and older who have symptomatic heart failure 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 benefits of Entresto (sacubitril/valsartan) include:

  • Reducing the risk of death and hospitalization in adults with chronic heart failure
  • Improving cardiovascular outcomes in pediatric patients aged one year and older with symptomatic heart failure
  • Reducing the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure and reduced ejection fraction
  • Treating symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older 2 2

From the Research

Benefits of Entresto (Sacubitril/Valsartan)

The benefits of Entresto (sacubitril/valsartan) include:

  • Reduction in cardiovascular mortality and heart failure hospitalization in patients with heart failure with reduced ejection fraction (HFrEF) 3, 4, 5
  • Reduction in all-cause mortality 3, 4, 6
  • Improvement in cardiac remodeling and quality of life 5
  • Reduction in disease progression 5
  • Improvement in left ventricular ejection fraction (LVEF) 6
  • Reduction in hospitalizations 6

Mechanisms of Action

The mechanisms of action of sacubitril/valsartan include:

  • Inhibition of neprilysin, an enzyme that degrades biologically active natriuretic peptides, resulting in increased levels of circulating natriuretic peptides 3, 5
  • Blockade of the angiotensin receptor, resulting in vasodilatory effects 3, 5
  • Impact on the renin-angiotensin-aldosterone system (RAAS) and the natriuretic peptide (NP) system 5

Patient Populations

Sacubitril/valsartan has been shown to be beneficial in various patient populations, including:

  • Patients with HFrEF 3, 4, 5
  • Patients with coexisting end-stage renal disease (ESRD) 6
  • Patients with type 2 diabetes mellitus 5

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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