What are the target doses for each medication in the treatment of resistant hypertension?

Target Doses for Resistant Hypertension Medications

Foundation Triple Therapy (Maximal or Maximally Tolerated Doses)

For resistant hypertension, the foundation regimen must include a renin-angiotensin system blocker, a long-acting calcium channel blocker, and a thiazide-like diuretic—all at maximal or maximally tolerated doses before considering the diagnosis of true treatment resistance. 1

Renin-Angiotensin System Blocker

• ACE inhibitors or ARBs should be titrated to the maximum tolerated dose indicated for blood pressure treatment 2
• Common target doses include:
  • Lisinopril: 40 mg daily
  • Enalapril: 20-40 mg daily (divided doses)
  • Losartan: 100 mg daily
  • Candesartan: 32 mg daily 3

Thiazide-Like Diuretic (Preferred Over Standard Thiazides)

• Chlorthalidone or indapamide are preferred over hydrochlorothiazide due to superior efficacy in resistant hypertension 2, 1
• Target doses:
  • Chlorthalidone: 12.5-25 mg daily
  • Indapamide: 1.25-2.5 mg daily 2
• Switch to loop diuretics (furosemide 40-80 mg daily or higher) if eGFR <30 mL/min/1.73m² or volume overload is present 1

Dihydropyridine Calcium Channel Blocker

• Target doses:
  • Amlodipine: 10 mg daily
  • Nifedipine extended-release: 60-90 mg daily 3

Fourth-Line Agent: Mineralocorticoid Receptor Antagonist

Spironolactone is the preferred fourth-line agent for resistant hypertension, demonstrating superior efficacy compared to other options. 1, 4

Spironolactone Dosing

• Starting dose: 25 mg once daily 1
• Target dose: 25-50 mg once daily 2
• Monitor serum potassium and renal function 1-2 weeks after initiation 1
• Use caution if eGFR <30 mL/min/1.73m² due to hyperkalemia risk 1

Eplerenone (Alternative to Spironolactone)

• For hypertension: Starting dose 50 mg once daily 5
• For inadequate response: Increase to 50 mg twice daily (maximum 100 mg daily) 5
• Higher doses not recommended due to increased hyperkalemia risk without additional BP benefit 5
• If using with moderate CYP3A inhibitors: Start at 25 mg once daily, maximum 25 mg twice daily 5
• Measure serum potassium before initiation, within first week, at one month, and periodically thereafter 5

Alternative Fourth-Line Agents (If Spironolactone/Eplerenone Contraindicated)

When mineralocorticoid receptor antagonists cannot be used, consider these alternatives at target doses 4:

• Amiloride: 5-10 mg daily
• Doxazosin: 4-8 mg daily
• Beta-blockers (if not already prescribed for another indication)
• Clonidine: 0.1-0.3 mg twice daily

Critical Monitoring Parameters

• Reassess BP response within 2-4 weeks of any medication adjustment 1
• Check serum potassium and renal function regularly, especially after adding mineralocorticoid receptor antagonists 2, 1
• For patients on ACE inhibitor/ARB/diuretic combinations: Monitor serum creatinine/eGFR and potassium at least annually 2

Important Caveats

• Dose adjustments for eplerenone based on potassium levels: If potassium 5.5-5.9 mEq/L, reduce from 50 mg to 25 mg daily; if ≥6.0 mEq/L, withhold until <5.5 mEq/L 5
• Combining mineralocorticoid receptor antagonists with ACE inhibitors or ARBs increases hyperkalemia risk—vigilant monitoring is essential 2
• Single-pill combination formulations should be used when available to improve adherence 1