What are the indications and dosing guidelines for Spironolactone (aldosterone antagonist) in patients with heart failure, hypertension, and edema?

Spironolactone: Indications and Dosing Guidelines for Heart Failure, Hypertension, and Edema

Spironolactone is indicated for NYHA Class III-IV heart failure with reduced ejection fraction (HFrEF) to improve survival, for resistant hypertension as add-on therapy, and for edema associated with hepatic cirrhosis or nephrotic syndrome when other treatments are inadequate. 1

Heart Failure Indications

Patient Selection

• LVEF ≤35% 2
• Moderate to severe symptoms (NYHA functional class III-IV) 2, 1
• Patients should be on optimal doses of:
  • ACE inhibitor or ARB 2
  • Beta-blocker 2
  • Loop diuretic 1

Dosing for Heart Failure

• Starting dose: 25 mg once daily 2, 3
• Target dose: 25-50 mg once daily 2, 3
• Consider dose up-titration after 4-8 weeks if tolerated 2
• For elderly or those with renal concerns, may start at 25 mg on alternate days 2

Hypertension Indications

• Add-on therapy for resistant hypertension 3, 1
• Effective at doses ranging from 25-100 mg/day 1
• Doses greater than 100 mg/day generally do not provide additional blood pressure reduction 1

Edema Management

• Indicated for edema associated with hepatic cirrhosis when not responsive to fluid/sodium restriction 1
• Indicated for nephrotic syndrome when other treatments are inadequate 1
• Particularly useful when other diuretics have caused hypokalemia 1

Monitoring Requirements

Before Initiation

• Check renal function and serum electrolytes 2
• Ensure potassium <5.0 mEq/L 4
• Ensure eGFR >30 mL/min/1.73m² 4

After Initiation

• Recheck renal function and electrolytes at 1 and 4 weeks 2, 3
• Then at 1,2,3, and 6 months after achieving maintenance dose 2
• Continue monitoring every 6 months thereafter 2

Dose Adjustment for Adverse Effects

Hyperkalemia

• If K+ rises to >5.5 mmol/L: Halve dose (e.g., to 25 mg on alternate days) 2
• If K+ rises to >6.0 mmol/L: Stop spironolactone immediately 2

Renal Dysfunction

• If creatinine rises to >220 μmol/L (2.5 mg/dL): Halve dose 2
• If creatinine rises to >310 μmol/L (3.5 mg/dL): Stop spironolactone immediately 2

Common Adverse Effects

• Hyperkalemia (3.3% vs 1.4% in non-users) 5
• Gynecomastia (10% in RALES trial) 2, 5
• Breast discomfort in men 2
• Menstrual irregularities in women 6
• Decreased libido and impotence in men 6

Clinical Pearls and Pitfalls

• Compliance issues: Treatment adherence with spironolactone (45.6%) is significantly lower than with ACE inhibitors (56.1%), β-blockers (59.7%), and ARBs (57.0%) 5
• Drug interactions: Use caution when combining with ACE inhibitors, ARBs, other potassium-sparing diuretics, potassium supplements, and NSAIDs 2
• Elderly patients: Often receive lower doses (median ~20 mg/day) but still benefit from treatment 7
• Alternative options: Consider eplerenone for men with painful gynecomastia or breast discomfort 2, 3
• Low-dose strategy: In patients unable to tolerate target doses, a low-dose strategy is preferable to stopping treatment completely 7

Efficacy Evidence

• The RALES study demonstrated a 30% reduction in mortality and 35% reduction in hospitalizations for worsening heart failure in patients with severe HF 2
• The absolute risk reduction in mortality was 11.4%, equating to a number needed to treat of 9 over 2 years 2
• Spironolactone reduces both death from progressive heart failure and sudden cardiac death 2
• In hypertension, spironolactone effectively controls blood pressure and hypokalemia in the majority of cases 6

By following these evidence-based guidelines for spironolactone use, clinicians can appropriately manage patients with heart failure, hypertension, and edema while minimizing adverse effects through careful monitoring and dose adjustments.