What is the role of Spironolactone (a potassium-sparing diuretic) in hypertension management?

Role of Spironolactone in Hypertension Management

Spironolactone is primarily indicated as an add-on therapy for resistant hypertension, providing significant blood pressure reduction when added to multi-drug regimens that have failed to achieve blood pressure control. 1, 2

Primary Indications for Spironolactone in Hypertension

Resistant Hypertension

• Defined as BP >140/90 mmHg despite treatment with ≥3 antihypertensive medications at optimal doses including a diuretic 1
• Recommended as 4th-line agent in resistant hypertension at doses of 25-100 mg daily 1
• Most effective when:
  • Serum potassium <4.5 mmol/L
  • eGFR >45 ml/min/1.73m² 1

Primary Aldosteronism

• Preferred agent for primary aldosteronism 1
• Used for:
  • Short-term preoperative treatment
  • Long-term maintenance therapy for patients with aldosterone-producing adenomas who aren't surgical candidates 2

Dosing and Efficacy

• Starting dose: 25 mg daily 1, 2
• Usual dose range: 25-100 mg daily 1
• Efficacy in resistant hypertension:
  • Average BP reduction: 21-26/10-12 mmHg when added to existing regimens 3, 4
  • Similar efficacy in patients with and without primary aldosteronism 3
  • Effects are additive to ACE inhibitors, ARBs, and diuretics 3

Mechanism of Action

Spironolactone works through:

• Competitive binding to aldosterone receptors in the distal convoluted renal tubule 2
• Blocking sodium-potassium exchange, causing increased sodium and water excretion while retaining potassium 2
• Counteracting secondary aldosteronism induced by volume depletion from other diuretics 2

Monitoring and Safety Considerations

Key Monitoring Parameters

• Serum potassium (risk of hyperkalemia)
• Renal function (serum creatinine)
• Blood pressure response

Contraindications/Cautions

• Avoid use with:
  • Potassium supplements
  • Other potassium-sparing diuretics
  • Significant renal dysfunction 1
  • Concomitant use of potent CYP3A4 inhibitors 1

Common Adverse Effects

• Hyperkalemia (most serious concern)
• Gynecomastia and impotence (more common with spironolactone than eplerenone) 1
• Headache, diarrhea, fatigue, decreased libido, menstrual disruption 1

Practical Approach to Using Spironolactone

1. Patient Selection:

   • Patients with resistant hypertension not controlled on ≥3 drugs including a diuretic
   • Patients with primary aldosteronism
   • Patients with hypokalemia on thiazide diuretics

2. Before Initiating:

   • Rule out pseudoresistance (poor BP measurement, white coat effect, nonadherence)
   • Check baseline potassium and renal function
   • Optimize current regimen including diuretic therapy

3. Dosing Strategy:

   • Start with 25 mg daily
   • May increase to 50 mg daily if needed and tolerated
   • Monitor BP response at 6 weeks, 3 months, and 6 months

4. Monitoring:

   • Check serum potassium and creatinine within 1-2 weeks of initiation
   • Monitor periodically thereafter, especially in patients with reduced renal function
   • Watch for clinical signs of adverse effects

Special Considerations

• Elderly patients: Use with caution; may be more susceptible to electrolyte disturbances
• Patients with diabetes: Higher risk of hyperkalemia; monitor more closely
• Patients with heart failure: Spironolactone has mortality benefit in HF with reduced ejection fraction 2
• Patients with CKD: Use with caution; increased risk of hyperkalemia

Spironolactone remains a valuable but often underutilized agent in hypertension management, particularly for resistant hypertension where it has demonstrated superior efficacy compared to other fourth-line agents 5.