What is the maximum dosage of heart failure medications such as Angiotensin-Converting Enzyme (ACE) inhibitors, beta-blockers, and Mineralocorticoid Receptor Antagonists (MRAs) like lisinopril, carvedilol, and spironolactone?

From the Guidelines

The maximum dosages for heart failure medications such as ACE inhibitors, beta-blockers, and Mineralocorticoid Receptor Antagonists (MRAs) should be titrated to the highest tolerated doses, with lisinopril up to 40 mg daily, carvedilol up to 25-50 mg twice daily, and spironolactone up to 50 mg daily, as recommended by the 2022 AHA/ACC/HFSA guideline 1.

Key Considerations for Dosing

• ACE inhibitors like lisinopril can be increased up to 40 mg daily, with most patients maintained on 20-40 mg daily, as shown in the 2022 guideline 1.
• Beta-blockers like carvedilol can be titrated to a maximum of 25 mg twice daily for patients weighing less than 85 kg, and 50 mg twice daily for those weighing more, according to the 2022 guideline 1.
• For MRAs, spironolactone is typically dosed at 25-50 mg daily, with 50 mg being the maximum recommended dose for most heart failure patients, as stated in the 2022 guideline 1.

Monitoring and Adjustments

• These medications should be started at lower doses and gradually increased every 2-4 weeks as tolerated, while monitoring blood pressure, heart rate, renal function, and electrolytes (particularly potassium) 1.
• Dose adjustments may be necessary for patients with renal impairment, low blood pressure, or electrolyte abnormalities, as recommended by the 2020 ACC/AHA clinical performance and quality measures for adults with heart failure 1.

Importance of Target Doses

• The goal of reaching target doses is important because clinical trials demonstrating mortality benefits used these higher doses, as shown in the 2022 guideline 1.
• However, some benefit is still achieved even at lower doses if maximum doses cannot be tolerated, so maintaining patients on the highest tolerated dose within this range is the recommended approach for optimizing heart failure outcomes, as stated in the 2020 ACC/AHA clinical performance and quality measures for adults with heart failure 1.

From the FDA Drug Label

DOSAGE & ADMINISTRATION 2. 2 Heart Failure The recommended starting dose for lisinopril tablets, when used with diuretics and (usually) digitalis as adjunctive therapy for systolic heart failure, is 5 mg once daily... Increase as tolerated to a maximum of 40 mg once daily. DOSAGE MUST BE INDIVIDUALIZED AND MONITORED DURING UP-TITRATION. ... The recommended dosing regimen ... 25 mg twice daily. Total daily dose should not exceed 50 mg. The maximum dosage of heart failure medications are:

• Lisinopril: 40 mg once daily 2
• Carvedilol: 50 mg total daily dose, divided into twice daily doses, with a maximum of 25 mg twice daily 3 Note: The maximum dosage of Spironolactone is not provided in the given drug labels.

From the Research

Maximum Dosage of Heart Failure Medications

The maximum dosage of heart failure medications such as Angiotensin-Converting Enzyme (ACE) inhibitors, beta-blockers, and Mineralocorticoid Receptor Antagonists (MRAs) can vary depending on the specific medication and patient population.

• ACE inhibitors: The study 4 found that women with heart failure with reduced ejection fraction (HFrEF) may reach optimal treatment effect at half of the guideline-recommended medication dose.
• Beta-blockers: The study 4 found that beta-blocker dose was not associated with all-cause mortality in patients with HFrEF.
• Mineralocorticoid Receptor Antagonists (MRAs): The study 4 found that patients received MRAs at a mean target dose of 100% across prescriptions.

Factors Affecting Maximum Dosage

Several factors can affect the maximum dosage of heart failure medications, including:

• Blood pressure: The study 5 found that blood pressure is one of the factors that may impede achieving target doses of all medications.
• Renal function: The study 5 found that renal function is one of the factors that may impede achieving target doses of all medications.
• Hyperkalaemia: The study 5 found that hyperkalaemia is one of the factors that may impede achieving target doses of all medications.
• Patient population: The study 4 found that women with HFrEF may require lower doses of ACE inhibitors than men.

Clinical Practice Guidelines

Clinical practice guidelines recommend using the same target dosing of therapies, as tolerated 5. However, the study 5 found that significant variability exists in dosing achieved in clinical practice.

• The study 6 found that the optimization of guideline-directed chronic HF therapy remains the mainstay to further improve outcomes for patients with HFrEF.
• The study 7 found that key considerations for older adults with HFpEF include the use of loop diuretics, MRAs, and SGLT2 inhibitors, as well as ARB/ARNIs and GLP-1RAs as add-on therapies.