What is the recommended dosage and treatment regimen for spironolactone (Aldactone) in patients with heart failure?

Spironolactone Dosing and Treatment Regimen for Heart Failure

For patients with heart failure, spironolactone should be initiated at 25 mg once daily in those with normal renal function, with potential titration to 50 mg daily as the maximum target dose based on clinical response and laboratory monitoring. 1, 2

Patient Selection

Spironolactone is indicated for:

• Patients with LVEF ≤35% 1
• Moderate to severe symptoms (NYHA class III-IV) 1
• Patients already on optimal therapy with ACE inhibitors and beta-blockers 1

Initial Dosing Protocol

1. Baseline Assessment:

   • Ensure serum potassium ≤5.0 mmol/L 1, 3
   • Verify adequate renal function (creatinine <220 μmol/L or 2.5 mg/dL) 1, 2
   • For patients with eGFR 30-50 mL/min/1.73m², consider starting at 25 mg every other day 2

2. Starting Dose:

   • 25 mg once daily for patients with normal renal function 1, 2
   • For patients with impaired renal function, consider 12.5 mg daily 3

Monitoring Schedule

Rigorous monitoring is essential to prevent complications:

• First month: Check renal function and electrolytes at 1 and 4 weeks after starting 1, 3
• Dose titration: Recheck 1 and 4 weeks after any dose change 1
• Maintenance: Monitor at 1,2,3, and 6 months after achieving maintenance dose, then every 6 months 1, 3

Dose Titration

• Consider dose up-titration after 4-8 weeks if the initial dose is well tolerated 1, 3
• Target dose: 50 mg once daily (if tolerated) 1
• Do not increase dose if there is worsening renal function or hyperkalemia 1

Managing Adverse Effects

Hyperkalemia

• If potassium rises to >5.5 mmol/L: Reduce dose by 50% (e.g., to 25 mg on alternate days) 1
• If potassium rises to ≥6.0 mmol/L: Stop spironolactone immediately 1

Worsening Renal Function

• If creatinine rises to >220 μmol/L (2.5 mg/dL): Reduce dose by 50% 1
• If creatinine rises to >310 μmol/L (3.5 mg/dL): Stop spironolactone immediately 1

Gynecomastia

• Occurs in approximately 10% of male patients 1
• Consider switching to eplerenone if this side effect occurs 1, 4

Clinical Evidence Supporting This Regimen

The RALES trial demonstrated that spironolactone at low doses (25-50 mg daily) reduced mortality by 30% and hospitalization for worsening heart failure by 35% in patients with severe heart failure 1. The absolute risk reduction in mortality was 11.4%, equating to a number needed to treat of 9 over 2 years 1.

Higher doses (>50 mg) have been studied in advanced heart failure but are generally not recommended due to increased risk of hyperkalemia 5. The ATHENA-HF trial showed that high-dose spironolactone (100 mg) did not improve outcomes compared to usual care 6.

Important Caveats

• Avoid use in patients with serum creatinine >2.5 mg/dL or potassium >5.0 mmol/L 1, 3
• Risk of hyperkalemia increases with higher doses, especially when combined with ACE inhibitors 7
• For patients unable to tolerate target doses, a low-dose strategy (even 12.5 mg) is preferable to discontinuation 8
• Eplerenone is an alternative for patients who develop gynecomastia on spironolactone, starting at 25 mg daily and titrating to 50 mg daily 4

Spironolactone should be used cautiously in elderly patients, those with renal dysfunction, and those with baseline potassium >4.5 mmol/L, as these groups typically receive lower doses (approximately 20 mg/day) and have higher discontinuation rates 8.