What is the recommended dose of spironolactone (aldosterone antagonist) for heart failure with reduced ejection fraction?

Spironolactone Dosing for Heart Failure with Reduced Ejection Fraction

The recommended starting dose of spironolactone for heart failure with reduced ejection fraction is 12.5 to 25 mg once daily, with a target maintenance dose of 50 mg once daily, provided careful monitoring of potassium and renal function is performed. 1

Initial Dosing Recommendations

• Start with 12.5 to 25 mg once daily if serum potassium is ≤5.0 mEq/L and eGFR ≥50 mL/min/1.73m² 1, 2
• For patients with marginal renal function (eGFR 30-49 mL/min/1.73m²), use a lower initial dose of 12.5 mg once daily or consider every-other-day dosing 1
• For elderly patients or those at higher risk of hyperkalemia, consider starting at 12.5 mg daily 2
• Spironolactone is contraindicated if serum creatinine is >2.5 mg/dL in men or >2.0 mg/dL in women (or eGFR <30 mL/min/1.73m²), or if potassium is >5.0 mEq/L 1

Dose Titration and Target Dose

• After 4 weeks, if potassium remains ≤5.0 mEq/L and renal function is stable, increase to the target maintenance dose of 50 mg once daily for patients with eGFR ≥50 mL/min/1.73m² 1
• For patients with eGFR 30-49 mL/min/1.73m², the maintenance dose should be 12.5-25 mg once daily 1
• The RALES trial demonstrated mortality benefit with spironolactone doses of 12.5-50 mg in patients with advanced heart failure 2, 3

Monitoring Requirements

• Check potassium and renal function within 2-3 days after initiation 1
• Recheck again at 7 days after initiation 1
• Continue monitoring monthly for the first 3 months and every 3 months thereafter 1
• Implement additional monitoring when adding or increasing doses of ACE inhibitors or ARBs 1
• If potassium rises to 5.0-5.5 mEq/L, consider reducing the dose by 50% 2
• If potassium exceeds 5.5 mEq/L, discontinue spironolactone immediately 2, 1

Precautions and Risk Management

• Discontinue potassium supplements when initiating spironolactone (or reduce and carefully monitor if patient has history of hypokalemia) 1
• Counsel patients to avoid foods high in potassium and NSAIDs 1
• Instruct patients to stop spironolactone during episodes of diarrhea, dehydration, or when loop diuretic therapy is interrupted 1
• The risk of hyperkalemia increases with:
  • Concomitant use of higher doses of ACE inhibitors 1
  • Baseline elevation of serum creatinine or potassium levels 3
  • Use of ACE inhibitors other than captopril 3
• Avoid routine triple combination of ACE inhibitors, ARBs, and spironolactone due to increased risk of hyperkalemia 1

Special Considerations

• At low doses (12.5-25 mg), spironolactone primarily acts as an aldosterone antagonist rather than as a diuretic 2
• Spironolactone can cause gynecomastia in men (approximately 10% of cases) 2
• For patients who cannot tolerate spironolactone, eplerenone is an alternative with similar dosing considerations but less anti-androgenic effects 1
• Higher doses of spironolactone (50 mg once daily) may provide greater benefits in reducing biomarkers of heart failure, but with increased risk of adverse effects 4

By following these dosing and monitoring recommendations, clinicians can optimize the benefits of spironolactone while minimizing the risks of hyperkalemia and renal dysfunction in patients with heart failure with reduced ejection fraction.