Purpose of Entresto (Sacubitril/Valsartan)
Entresto (sacubitril/valsartan) is primarily indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure with reduced ejection fraction (HFrEF), and for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older. 1
Mechanism of Action
- Entresto is a first-in-class angiotensin receptor-neprilysin inhibitor (ARNi) that combines two active components 2:
- Sacubitril: A neprilysin (NEP) inhibitor that prevents the breakdown of natriuretic peptides
- Valsartan: An angiotensin II receptor blocker (ARB) that blocks the harmful effects of the renin-angiotensin-aldosterone system
Clinical Indications
Adult Patients
- Recommended as a replacement for ACE inhibitors to further reduce the risk of heart failure hospitalization and death in ambulatory patients with HFrEF who remain symptomatic despite optimal treatment with an ACE inhibitor, a beta-blocker, and a mineralocorticoid receptor antagonist (MRA) 2
- Can be initiated in hospitalized patients with acute HFrEF before discharge to improve health status and reduce NT-proBNP levels 2
- May be used as de novo treatment in patients with symptomatic chronic HFrEF to simplify management 2
Pediatric Patients
- Indicated for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in children aged one year and older 1
- Reduces NT-proBNP levels and is expected to improve cardiovascular outcomes in this population 1
Clinical Benefits
- Significantly reduces the risk of cardiovascular death and heart failure hospitalization compared to ACE inhibitors (enalapril) in patients with HFrEF 2
- Improves symptoms and quality of life in patients with heart failure 2, 3
- May have potential antiarrhythmic effects, possibly reducing the risk of sudden cardiac death 4
- Demonstrated to reduce sympathetic nervous system activity in patients with HFrEF, which may contribute to its clinical benefits 5
- Benefits are consistent across different baseline systolic blood pressure categories, including in patients with low blood pressure 2
Practical Considerations
- The recommended starting dose for adults is 49 mg/51 mg orally twice daily, with a target maintenance dose of 97 mg/103 mg orally twice daily 1
- Dose adjustments are needed for patients with severe renal impairment or moderate hepatic impairment 1
- When switching from an ACE inhibitor to Entresto, a 36-hour washout period is required to reduce the risk of angioedema 1
- Not recommended in patients with severe hepatic impairment 1
Contraindications and Cautions
- Contraindicated in patients with 1:
- Hypersensitivity to any component
- History of angioedema related to previous ACE inhibitor or ARB therapy
- Concomitant use with ACE inhibitors
- Concomitant use with aliskiren in patients with diabetes
- Should be discontinued when pregnancy is detected due to potential fetal toxicity 1
- Breastfeeding is not recommended during treatment 1
- May interact with statins that are substrates of OATP1B1, OATP1B3, OAT1, and OAT3 transporters 2
Monitoring
- Observe for signs and symptoms of angioedema and hypotension 1
- Monitor renal function and potassium levels, especially in susceptible patients 1
- Common adverse reactions include hypotension, hyperkalemia, cough, dizziness, and renal failure 1
Entresto represents a significant advancement in heart failure therapy, offering improved outcomes compared to traditional ACE inhibitor therapy in patients with HFrEF.