What are the guidelines for initiating Entresto (sacubitril/valsartan) in patients with chronic heart failure in the UK?

From the Guidelines

In the UK, Entresto (sacubitril/valsartan) is recommended for chronic heart failure patients with reduced ejection fraction (HFrEF) who have NYHA class II-IV symptoms, a left ventricular ejection fraction of 35% or less, and who are already stabilized on an ACE inhibitor or ARB, with a starting dose of 49/51 mg twice daily, as per the most recent guidelines 1.

Key Considerations

• The patient should have adequate blood pressure (typically systolic BP >100 mmHg), reasonable kidney function (eGFR ≥30 ml/min/1.73m²), and serum potassium ≤5.4 mmol/L before initiating Entresto.
• ACE inhibitors must be discontinued for at least 36 hours to avoid angioedema risk.
• Regular monitoring of blood pressure, renal function, and electrolytes is essential, particularly during dose titration.

Dosing and Titration

• The starting dose is typically 49/51 mg twice daily (or 24/26 mg twice daily for patients not currently taking an ACE inhibitor/ARB, elderly patients, or those with severe renal impairment) 1.
• The target dose is 97/103 mg twice daily, with dose titration at 2-4 week intervals, as tolerated by the patient.

Mechanism of Action

• Entresto works by combining neprilysin inhibition (sacubitril) with angiotensin receptor blockade (valsartan), enhancing beneficial neurohormonal pathways while blocking harmful ones, which improves cardiac function and reduces hospitalizations and mortality in heart failure patients.

Guideline Recommendations

• The 2022 AHA/ACC/HFSA guideline for the management of heart failure recommends the use of Entresto for patients with HFrEF, with a class I indication for patients with NYHA class II-IV symptoms and a left ventricular ejection fraction of 35% or less 1.
• The European Journal of Heart Failure also recommends the use of Entresto for patients with HFrEF, with a focus on optimizing medical therapy and improving patient outcomes 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Guidelines for Starting Chronic Heart Failure Patients on Sacubitril/Valsartan in the UK

• The guidelines for starting chronic heart failure patients on sacubitril/valsartan in the UK are based on the patient's condition and medical history 2, 3, 4, 5, 6.
• Sacubitril/valsartan is recommended as an alternative to angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) to lower morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF) 2, 3.
• The ENTRESTO-SAS study found that sacubitril/valsartan treatment for 3 months in sleep apnea patients is associated with a significant decrease in apnea-hypopnea index (AHI) 4.
• A meta-analysis of randomized controlled trials found that sacubitril/valsartan reduced the risk of all-cause mortality, cardiovascular mortality, and hospitalization for heart failure in patients with HFrEF 3, 5.
• The medication is also associated with a high risk of symptomatic hypotension, but a low risk of worsening renal function and serious hyperkalaemia 3, 5.
• Real-world studies have shown that sacubitril/valsartan is superior to ARB therapy in reducing the occurrence of cardiovascular death and hospitalization for worsening heart failure in patients with HFrEF 6.

Key Considerations

• Patients with chronic heart failure should be evaluated for sacubitril/valsartan treatment based on their individual needs and medical history 2, 3, 4, 5, 6.
• The treatment should be initiated and monitored by a healthcare professional to minimize the risk of adverse events 3, 5.
• Patients should be educated on the potential benefits and risks of sacubitril/valsartan treatment and monitored regularly for any changes in their condition 2, 3, 4, 5, 6.