What is the appropriate dosing of spironolactone (an aldosterone antagonist) for a patient with anasarca, heart failure with preserved ejection fraction (EF), and sarcoidosis?

From the Guidelines

For a patient with anasarca, heart failure with preserved ejection fraction (HFpEF), and sarcoidosis, spironolactone should be initiated at 12.5-25 mg once daily and can be titrated up to 50 mg daily as needed, based on clinical response and laboratory monitoring, as suggested by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.

Key Considerations

• Start at the lower dose (12.5 mg) for patients with renal impairment or those at higher risk of hyperkalemia.
• Monitor serum potassium, sodium, and renal function at baseline, within 1 week of initiation, and regularly thereafter (every 1-4 weeks during dose adjustments, then monthly to quarterly once stable).
• Spironolactone works as an aldosterone antagonist to reduce fluid retention and may improve outcomes in HFpEF by decreasing myocardial fibrosis and vascular stiffness.

Important Interactions and Precautions

• For patients with anasarca, consider combining spironolactone with loop diuretics like furosemide for enhanced diuresis.
• Be cautious of hyperkalemia, especially if the patient is on ACE inhibitors or ARBs.
• In sarcoidosis patients, monitor for potential interactions with corticosteroids or other immunosuppressants they may be taking.
• Adjust the dose downward if serum creatinine increases significantly or if potassium exceeds 5.5 mEq/L.

Evidence Base

The use of spironolactone in HFpEF is supported by the TOPCAT trial, which showed a reduction in HF hospitalization, although the composite endpoint of death, aborted cardiac death, and HF hospitalization was not statistically significant 1.

Patient Selection

Appropriately selected patients with symptomatic HFpEF (LVEF ≥45%, elevated BNP level or HF admission within 1 year, eGFR >30 mL/min/1.73 m², creatinine <2.5 mg/dL, and potassium <5.0 mEq/L) may benefit from spironolactone, with careful monitoring of potassium, renal function, and diuretic dosing 1.

From the FDA Drug Label

2.2 Treatment of Heart Failure In patients with serum potassium ≤ 5.0 mEq/L and eGFR > 50 mL/min/1. 73 m 2, initiate treatment at 25 mg once daily. Patients who tolerate 25 mg once daily may have their dosage increased to 50 mg once daily as clinically indicated. In patients with an eGFR between 30 and 50 mL/min/1. 73 m 2, consider initiating therapy at 25 mg every other day because of the risk of hyperkalemia

The patient has anasarca and heart failure with preserved EF and sarcoidosis. For heart failure, the dosing of spironolactone is as follows:

• If the patient has serum potassium ≤ 5.0 mEq/L and eGFR > 50 mL/min/1.73 m^2, initiate treatment at 25 mg once daily.
• The dosage can be increased to 50 mg once daily as clinically indicated.
• If the patient has an eGFR between 30 and 50 mL/min/1.73 m^2, consider initiating therapy at 25 mg every other day due to the risk of hyperkalemia. 2

From the Research

Patient with Anasarca and Heart Failure with Preserved EF and Sarcoidosis

Dosing of Spironolactone

• The dosing of spironolactone in patients with heart failure with preserved ejection fraction (HFpEF) and sarcoidosis is not directly addressed in the provided studies 3, 4, 5, 6, 7.
• However, the studies suggest that spironolactone may be beneficial in reducing morbidity and mortality in patients with HFpEF 3, 7.
• The ATHENA-HF trial found that high-dose spironolactone did not improve congestion over usual care among patients with acute HF, irrespective of renal function and risk factors for diuretic resistance 4.
• A study published in the European Journal of Clinical Pharmacology found that spironolactone may be safe to initiate in hospitalized patients with HF and chronic kidney disease, but larger studies are needed for conclusive results 5.
• The TOPCAT Americas analysis found that the benefit of spironolactone on outcomes could not be solely attributed to potential diuretic effects, suggesting the presence of non-diuretic mechanisms 7.

Considerations for Dosing

• Patients with HFpEF and sarcoidosis should be closely monitored for signs of hyperkalemia, as spironolactone can increase the risk of hyperkalemia, particularly in patients with renal dysfunction 4, 5.
• The dosing of spironolactone should be individualized based on the patient's renal function, potassium levels, and other comorbidities 4, 5.
• Regular monitoring of serum potassium and creatinine levels is recommended to minimize the risk of hyperkalemia and renal dysfunction 4, 5.