What are the alternatives to Entresto (sacubitril/valsartan) 24-26 mg for patients with heart failure?

Alternatives to Entresto 24-26 mg for Heart Failure

For patients who cannot take Entresto (sacubitril/valsartan) 24-26 mg, the best alternatives are ACE inhibitors or ARBs, specifically starting with low doses such as captopril 6.25 mg three times daily, enalapril 2.5 mg twice daily, or valsartan 20-40 mg once daily. 1

First-Line Alternatives

ACE Inhibitors

ACE inhibitors are the primary alternative to Entresto for heart failure with reduced ejection fraction (HFrEF):

• Captopril: Start with 6.25 mg three times daily, target 50 mg three times daily
• Enalapril: Start with 2.5 mg twice daily, target 10-20 mg twice daily
• Lisinopril: Start with 2.5-5 mg once daily, target 20-40 mg once daily
• Ramipril: Start with 1.25-2.5 mg once daily, target 10 mg once daily

ACE inhibitors reduce mortality and morbidity in HFrEF and should be started at low doses and titrated upward to doses shown to reduce cardiovascular events in clinical trials 1.

Angiotensin Receptor Blockers (ARBs)

ARBs are recommended alternatives when ACE inhibitors are not tolerated:

• Valsartan: Start with 20-40 mg once daily, target 160 mg twice daily
• Candesartan: Start with 4-8 mg once daily, target 32 mg once daily
• Losartan: Start with 25-50 mg once daily, target 50-150 mg once daily

ARBs are particularly valuable for patients who experience cough or angioedema with ACE inhibitors 1.

Additional Foundational Therapies

Heart failure management requires multiple medication classes. In addition to ACE inhibitors or ARBs as alternatives to Entresto, these medications should be considered:

Beta-Blockers

• Bisoprolol: Start with 1.25 mg once daily, target 10 mg once daily
• Carvedilol: Start with 3.125 mg twice daily, target 25-50 mg twice daily
• Metoprolol succinate: Start with 12.5-25 mg once daily, target 200 mg once daily

Mineralocorticoid Receptor Antagonists (MRAs)

• Spironolactone: Start with 12.5-25 mg once daily, target 25-50 mg once daily
• Eplerenone: Start with 25 mg once daily, target 50 mg once daily

SGLT2 Inhibitors

• Dapagliflozin: 10 mg once daily
• Empagliflozin: 10 mg once daily

Special Considerations

For Patients with Very Low Blood Pressure

If the patient cannot tolerate Entresto 24-26 mg due to hypotension:

• Start with the lowest dose of ACE inhibitor (e.g., captopril 6.25 mg TID or enalapril 1.25 mg daily)
• Monitor blood pressure closely
• Titrate very gradually based on tolerance

For Patients with Renal Impairment

• For patients with CrCl <30 mL/min, start with lower doses of ACE inhibitors or ARBs
• Monitor renal function and potassium levels closely
• Consider dose reduction of other medications that may affect renal function

For Patients with Hyperkalemia Risk

• Choose eplerenone over spironolactone if MRA is needed
• Start with lower doses of ACE inhibitors or ARBs
• Monitor potassium levels more frequently

Practical Implementation

1. Start low, go slow: Begin with the lowest dose of the chosen alternative and titrate gradually
2. Monitor closely: Check blood pressure, renal function, and electrolytes 1-2 weeks after initiation and after each dose increase
3. Combination therapy: Add other heart failure medications (beta-blockers, MRAs, SGLT2i) as tolerated
4. Diuretic adjustment: Consider reducing diuretic dose if hypotension occurs with ACE inhibitor or ARB initiation

Common Pitfalls to Avoid

• Abrupt withdrawal: Never stop ACE inhibitors or ARBs suddenly as this can lead to clinical deterioration 1
• Inadequate dosing: Don't settle for low doses if higher doses are tolerated; aim for target doses used in clinical trials
• Failure to monitor: Always check renal function and potassium after starting or increasing doses
• Contraindications: Avoid ACE inhibitors and ARBs in pregnancy, bilateral renal artery stenosis, or history of angioedema
• Drug interactions: Be cautious with concomitant use of NSAIDs, potassium supplements, or potassium-sparing diuretics

By following these recommendations, clinicians can effectively manage patients with heart failure who cannot take Entresto 24-26 mg, while still optimizing outcomes related to mortality, morbidity, and quality of life.