Can spironolactone be used to treat hypertension (HTN)?

Spironolactone for Hypertension Management

Spironolactone is an effective medication for hypertension, particularly as add-on therapy for resistant hypertension, with strong evidence supporting its use as a fourth-line agent when blood pressure remains uncontrolled on three medications including a diuretic. 1

Indications for Spironolactone in Hypertension

Spironolactone is FDA-approved for the treatment of hypertension as add-on therapy to lower blood pressure in patients not adequately controlled on other agents 2. Its use in hypertension management can be categorized as follows:

As Standard Antihypertensive Therapy

• Classified as a potassium-sparing diuretic in hypertension guidelines 1
• Considered a secondary agent in the ACC/AHA hypertension guidelines 1
• Typical dosing range: 25-100 mg daily 1

For Resistant Hypertension

• Recommended as the fourth-line agent in patients with resistant hypertension after optimizing a three-drug regimen including a diuretic 1
• Most effective when added to patients whose serum potassium is <4.5 mmol/L and eGFR is >45 ml/min/1.73m² 1
• Provides significant additional blood pressure reduction (average 21-25/10-12 mmHg) when added to multidrug regimens 3, 4
• Superior to renal denervation for reducing 24-hour systolic and diastolic blood pressure in resistant hypertension 5

For Primary Aldosteronism

• Preferred agent for primary aldosteronism 1, 2
• Particularly effective in bilateral adrenal disease not amenable to surgery 1
• Effective in patients with resistant hypertension regardless of primary aldosteronism status 3

Dosing Considerations

• Starting dose: 25 mg daily 1, 2
• Low doses (12.5-25 mg) can be effective in resistant hypertension 3
• Can be titrated up to 50-100 mg daily if needed 2, 3
• Doses greater than 100 mg/day generally do not provide additional blood pressure reduction 2

Monitoring and Precautions

• Regular monitoring required for:

  • Serum potassium (risk of hyperkalemia)
  • Renal function (can cause acute kidney injury)
  • Side effects (gynecomastia, impotence in men)

• Contraindications/Cautions:

  • Avoid in patients with significant renal dysfunction (eGFR <45 ml/min) 1
  • Use cautiously with other potassium-sparing medications or potassium supplements 1
  • Avoid in patients with severe bilateral renal artery stenosis 1

Advantages Over Other Agents

• More effective than other fourth-line agents for resistant hypertension (demonstrated in PATHWAY-2 trial) 1
• Provides additional benefit even when combined with ACE inhibitors, ARBs, and diuretics 3
• Beneficial in patients with heart failure with reduced ejection fraction 2
• Effective in both African American and white patients with resistant hypertension 3

Alternative Options When Spironolactone is Not Tolerated

If spironolactone cannot be used due to side effects or contraindications, alternatives include:

• Eplerenone (less risk of hormonal side effects but less potent and requires twice-daily dosing) 1
• Amiloride 1, 6
• Other options: doxazosin, clonidine, or beta-blockers 1

Clinical Pearls

• Spironolactone's antihypertensive effect is often seen within 6 weeks of initiation 3
• The blood pressure-lowering effect persists at 6 months of follow-up 3
• Consider screening for primary aldosteronism in resistant hypertension before initiating spironolactone 1
• Newer non-steroidal MRAs (esaxerenone, finerenone) may offer alternatives with fewer side effects in the future 1

Spironolactone remains an underutilized but highly effective option for managing hypertension, particularly in the resistant hypertension setting where it should be considered before more invasive approaches 7, 5.