What is the comparative efficacy of spironolactone (aldosterone antagonist) vs eplerenone (selective aldosterone antagonist) in managing ascites?

Spironolactone is Superior to Eplerenone for Managing Ascites in Cirrhosis

Spironolactone should be used as first-line therapy for ascites management in cirrhosis, while eplerenone lacks sufficient evidence to support its use despite potentially having fewer androgenic side effects. 1

Comparative Efficacy of Spironolactone vs. Eplerenone

Evidence Base

• Spironolactone has robust evidence supporting its efficacy in ascites management with decades of clinical experience and guideline recommendations 1
• Eplerenone has limited evidence in cirrhotic ascites - the 2021 AASLD practice guidance specifically notes that eplerenone "has not been studied in the setting of cirrhosis and ascites" 1
• Only one small comparative study (n=105) has directly compared these medications, showing equal efficacy between spironolactone 100mg and eplerenone 100mg in managing ascites, but inferior results with eplerenone 50mg 2

Mechanism Considerations

• Both medications are aldosterone antagonists:
  • Spironolactone: Non-selective aldosterone antagonist
  • Eplerenone: Selective aldosterone antagonist with less binding to progesterone and androgen receptors

Treatment Algorithm for Ascites Management

First-Line Approach

1. Start with spironolactone 100 mg/day 1, 3
2. Implement moderate sodium restriction (2g or 90 mmol/day) 1
3. Titrate spironolactone dose upward in 100mg increments every 3-5 days as needed, up to maximum 400 mg/day 1
4. If inadequate response to maximum spironolactone, add furosemide 40 mg/day (can increase up to 160 mg/day) 1

Special Considerations

• For patients with painful gynecomastia on spironolactone:
  • Consider switching to amiloride (10-40 mg/day) 1
  • Eplerenone may be considered as an alternative, though evidence is limited 1, 2
• For tense ascites:
  • Initial large-volume paracentesis with albumin replacement (8g/L of fluid removed)
  • Resume diuretic therapy afterward to prevent reaccumulation 1

Side Effect Comparison

Spironolactone

• Gynecomastia (14.28% in comparative study) 2
• Sexual dysfunction and menstrual irregularities 1
• Hyperkalemia (2.8% in comparative study) 2

Eplerenone

• No reported gynecomastia in comparative study 2
• No reported hyperkalemia in comparative study 2
• Less endocrine side effects due to selective aldosterone receptor binding

Clinical Caveats and Monitoring

• Monitor serum electrolytes, especially potassium, and renal function regularly
• Discontinue diuretics if:
  • Serum sodium <120-125 mmol/L
  • Serum creatinine >2.0 mg/dL
  • Development of hepatic encephalopathy 1, 3
• Avoid NSAIDs, ACE inhibitors, and angiotensin receptor blockers as they can reduce diuretic effectiveness and worsen renal function 3

Bottom Line

While the single comparative study suggests eplerenone may have a better side effect profile than spironolactone 2, the overwhelming evidence and guideline recommendations support spironolactone as first-line therapy for ascites management in cirrhosis 1, 3. Eplerenone should be reserved for patients who develop significant androgenic side effects from spironolactone but still require aldosterone antagonism. More research is needed to definitively establish eplerenone's role in ascites management.