Is spironolactone (aldosterone antagonist) superior to furosemide (Lasix) in the management of portal hypertension?

Spironolactone vs. Furosemide in Portal Hypertension

Spironolactone is superior to furosemide (Lasix) in the management of portal hypertension due to its higher efficacy in treating ascites (95% vs 52% response rate) and its direct effect on reducing hepatic venous pressure gradient. 1

Mechanism of Action and Efficacy

Spironolactone

• Acts as a specific aldosterone antagonist at the distal convoluted tubule
• Addresses the underlying pathophysiology of portal hypertension by counteracting secondary aldosteronism, which plays a major role in renal sodium retention in cirrhosis 1
• Demonstrated to directly reduce hepatic venous pressure gradient (HVPG) in patients with cirrhosis 2, 3
• Achieves a response rate of 95% in non-azotemic patients with cirrhosis and ascites 1
• Can produce a significant reduction in HVPG even in patients without ascites through plasma volume contraction 3

Furosemide (Lasix)

• Loop diuretic acting primarily on the ascending limb of the loop of Henle
• Lower response rate of only 52% when used alone in non-azotemic patients with cirrhosis and ascites 1, 4
• Can cause acute reductions in glomerular filtration rate when administered intravenously 1
• Does not significantly reduce total blood volume or HVPG when used alone 3

Evidence-Based Treatment Approach

First-Line Treatment

• Start with spironolactone 100 mg daily as monotherapy for initial management 1
• Spironolactone alone has been shown to be as effective as combination therapy for moderate ascites with fewer dose adjustments needed (34% vs 68%) 5
• Gradually increase dose up to 400 mg daily if needed, with dose adjustments every 3-5 days based on response 1

Adding Furosemide

• Add furosemide only if inadequate response to maximum spironolactone dose 1
• Initial furosemide dose of 40 mg daily, can be increased up to 160 mg daily 1
• Maintain spironolactone:furosemide ratio of 100 mg:40 mg to maintain normokalemia 1

Monitoring Parameters

• Weight loss (target: 0.5 kg/day without peripheral edema, 1 kg/day with peripheral edema) 1
• Serum electrolytes, particularly potassium and sodium
• Renal function (serum creatinine)
• Urinary sodium excretion (target >78 mmol/day) 1

Special Considerations

Adverse Effects

• Spironolactone: Hyperkalemia, gynecomastia, menstrual irregularities, decreased libido
• Furosemide: Hypokalemia, hyponatremia, metabolic alkalosis, acute renal impairment

Cautions

• Stop diuretics if serum sodium ≤120 mmol/L 1
• Consider reducing or temporarily withholding diuretics if serum sodium 121-125 mmol/L 1
• Temporarily withhold furosemide in patients presenting with hypokalemia (common in alcoholic hepatitis) 1
• Reduce spironolactone dose in patients with parenchymal renal disease due to risk of hyperkalemia 1

Management of Refractory Cases

• For patients with tense ascites not responding to diuretics, large-volume paracentesis with albumin infusion is recommended 1
• In propranolol-resistant portal hypertension, spironolactone alone or in combination with propranolol can achieve adequate reduction in HVPG 2
• Spironolactone may be effective as part of triple therapy with beta-blockers and nitrates in difficult cases 6

Conclusion

Based on the most recent and highest quality evidence, spironolactone is clearly superior to furosemide as first-line therapy for portal hypertension due to its higher efficacy in treating ascites and direct effects on reducing portal pressure. The 2021 guidelines from Gut journal confirm this superiority with a 95% vs 52% response rate in favor of spironolactone 1.