When to initiate spironolactone (aldosterone antagonist) therapy?

From the Guidelines

Spironolactone therapy should be initiated in patients with HFrEF and NYHA class II to IV symptoms, with an eGFR >30 mL/min/1.73 m2 and serum potassium <5.0 mEq/L, as recommended by the 2022 AHA/ACC/HFSA guideline 1.

Key Considerations for Initiation

• Serum potassium levels should be checked to ensure they are <5.0 mEq/L before initiating spironolactone therapy
• Renal function, specifically eGFR, should be assessed to ensure it is >30 mL/min/1.73 m2
• The starting dose of spironolactone is 25 mg orally daily, which can be increased to 50 mg daily orally after a month
• For patients with an eGFR between 31 to 49 mL/min/1.73 m2, the dosing should be reduced by half

Monitoring After Initiation

• Regular checks of serum potassium levels and renal function should be performed approximately 1 week, then 4 weeks, and every 6 months after initiating or intensifying MRA therapy
• More frequent testing should be done in cases of clinical instability
• Patients should be counseled to avoid foods high in potassium and NSAIDs, and potassium supplementation should be discontinued or reduced and carefully monitored

Rationale

The recommendation to initiate spironolactone therapy in patients with HFrEF and NYHA class II to IV symptoms is based on the findings of several clinical trials, including RALES, EPHE SUS, and EMPHASIS-HF, which suggest a benefit of MRA therapy in reducing morbidity and mortality 1. The economic value of MRA therapy has also been assessed, with a model-based analysis finding that therapy is high value with a cost per QALY of under $1000 1.

From the FDA Drug Label

In patients with hepatic disease with cirrhosis and ascites. In these patients, initiate spironolactone in the hospital [see Dosage and Administration (2.4) and Clinical Pharmacology (12. 3)] . Clearance of spironolactone and its metabolites is reduced in patients with cirrhosis. In patients with cirrhosis, start with lowest initial dose and titrate slowly [ see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)] .

Initiation of Spironolactone Therapy:

• In patients with hepatic disease with cirrhosis and ascites, initiate spironolactone therapy in the hospital.
• In patients with cirrhosis, start with the lowest initial dose and titrate slowly. 2

From the Research

Initiation of Spironolactone Therapy

• Spironolactone therapy can be initiated in patients with heart failure, but careful consideration of renal function and potassium levels is necessary 3, 4, 5, 6, 7.
• Patients with renal impairment or hyperkalemia may require lower doses of spironolactone or more frequent monitoring of potassium levels 3, 4, 5, 6, 7.
• The safety and tolerability of spironolactone in patients with chronic kidney disease (CKD) have been evaluated, and the results suggest that spironolactone may be safe to initiate in hospitalized patients with heart failure and CKD, but larger studies are needed for conclusive results 7.

Patient Selection and Monitoring

• Patients with an estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2 and potassium < 5.0 mEq/L are generally considered suitable for spironolactone therapy 7.
• Patients with CKD stages 3-5 may require careful monitoring of potassium levels and renal function when initiating spironolactone therapy 5, 7.
• Regular monitoring of serum potassium, urea, and creatinine is recommended, particularly in the first month of treatment 3, 5.

Dosing and Titration

• The initial dose of spironolactone can be 25 mg daily, with titration to higher doses as needed and tolerated 3, 4.
• Patients with renal impairment or hyperkalemia may require lower doses of spironolactone, such as 12.5 mg daily 3, 6.
• The dose of spironolactone should be adjusted based on serum potassium levels and renal function, with a goal of minimizing the risk of hyperkalemia 3, 4, 5, 6, 7.