When to initiate Entresto (sacubitril/valsartan) therapy?

From the Guidelines

Entresto (sacubitril/valsartan) should be started in patients with chronic heart failure with reduced ejection fraction (HFrEF) who have an ejection fraction of 40% or less and are experiencing symptoms despite optimal medical therapy, with a recommended starting dose of 24/26 mg twice daily for most patients, which can be titrated to a target dose of 97/103 mg twice daily as tolerated, as supported by the most recent guidelines 1. When initiating Entresto, it is crucial to consider the patient's current medication regimen, particularly the use of ACE inhibitors or ARBs, as Entresto is intended to replace these medications.

• The patient should discontinue ACE inhibitors at least 36 hours prior to starting Entresto to avoid the risk of angioedema, as highlighted in the guidelines 1.
• Entresto is contraindicated in pregnancy, patients with a history of angioedema, and those with severe hepatic impairment.
• Lower starting doses (24/26 mg twice daily) are recommended for patients not currently taking an ACE inhibitor or ARB, those with severe renal impairment (eGFR <30 mL/min/1.73m²), or moderate hepatic impairment, as indicated in the guidelines 1. The mechanism of action of Entresto, which involves simultaneously inhibiting neprilysin and blocking angiotensin II receptors, helps reduce cardiac workload, improve cardiac output, and decrease mortality in heart failure patients, as demonstrated in clinical trials 1. Key considerations for the use of Entresto include:
• Monitoring for signs of angioedema, such as swelling of the face, lips, tongue, or throat, and hypotension, as these are potential side effects of the medication 1.
• Adjusting the dose of Entresto based on the patient's tolerance and response to treatment, with the goal of achieving the target dose of 97/103 mg twice daily, as recommended in the guidelines 1.
• Regular follow-up with a healthcare provider to assess the effectiveness of Entresto and adjust the treatment plan as needed, taking into account the patient's overall clinical status and any changes in their condition 1.

From the FDA Drug Label

The recommended starting dose of sacubitril and valsartan tablet is 49/51 mg orally twice-daily. In adults and pediatric patients with severe renal impairment estimated glomerular filtration rate (eGFR less than 30 mL/min/1. 73 m2), start sacubitril and valsartan tablets at half the usually recommended starting dose. In adults and pediatric patients with moderate hepatic impairment (Child-Pugh B classification), start sacubitril and valsartan tablets at half the usually recommended starting dose.

Starting Entresto:

• The recommended starting dose is 49/51 mg orally twice-daily.
• For patients with severe renal impairment, start at half the recommended dose.
• For patients with moderate hepatic impairment, start at half the recommended dose.
• A 36-hour washout period is required when switching from an ACE inhibitor to sacubitril and valsartan tablets 2.

From the Research

Entresto Treatment Timing

• The decision of when to start Entresto should be based on individual patient needs and medical history, as there is no one-size-fits-all answer 3, 4, 5, 6, 7.
• For patients with heart failure with reduced ejection fraction (HFrEF), Entresto can be considered as a replacement for ACE inhibitors or ARBs, as it has been shown to improve cardiovascular outcomes 4, 6.
• In patients with advanced heart failure, Entresto may be initiated after a period of stabilization with other treatments, such as diuretics and beta-blockers 5.
• The LIFE trial suggests that Entresto can be safely initiated in patients with advanced HFrEF, with a dose titration period to minimize the risk of hypotension 5.
• Real-world experience has shown that Entresto can be effective in patients with HFrEF, including those with advanced chronic kidney disease and hypotension, although dose escalation should be done cautiously 7.

Patient Selection

• Entresto is indicated for patients with HFrEF, with a left ventricular ejection fraction (LVEF) of 40% or less 3, 4, 5, 6, 7.
• Patients with heart failure with preserved ejection fraction (HFpEF) may also benefit from Entresto, although the evidence is less clear-cut 3.
• Patients with significant renal impairment or hypotension should be closely monitored when initiating Entresto, as they may be at increased risk of adverse effects 5, 7.

Dosing and Titration

• The recommended starting dose of Entresto is 49/51 mg twice daily, with titration to a target dose of 97/103 mg twice daily 5.
• Dose escalation should be done gradually, with close monitoring of blood pressure and renal function 5, 7.
• Patients who experience hypotension or other adverse effects may require dose reduction or discontinuation of Entresto 5, 7.