What to do for a 50-year-old male with resistant hypertension on valsartan (Angiotensin II Receptor Antagonist) 160 mg twice daily (bid), amlodipine (Calcium Channel Blocker) 10 mg once daily (od), selective beta-blocker and hydrochlorothiazide (Diuretic), whose blood pressure is still not controlled?

Management of Resistant Hypertension in a 50-Year-Old Male

For a 50-year-old male with resistant hypertension who is already on valsartan 160 mg twice daily, amlodipine 10 mg once daily, a selective beta-blocker, and hydrochlorothiazide, the addition of low-dose spironolactone (25-50 mg daily) to the existing regimen is strongly recommended as the next step in treatment. 1

Confirming Resistant Hypertension

Before adding another medication, ensure this is true resistant hypertension:

• Confirm BP readings using 24-hour ambulatory blood pressure monitoring or home BP monitoring to exclude white coat effect
• Verify medication adherence
• Assess for secondary causes of hypertension
• Review lifestyle factors (sodium intake, alcohol consumption, physical activity)

Treatment Algorithm

Step 1: Add Spironolactone

• Start with spironolactone 25 mg once daily 1
• Monitor serum potassium and renal function at baseline and within 1-2 weeks after initiation
• Titrate up to 50 mg daily if needed and tolerated
• Expected BP reduction: 20-25/10-12 mmHg 2

Step 2: If Spironolactone is Not Tolerated or Contraindicated

Consider these alternatives in sequence:

1. Eplerenone (50-100 mg daily) - better tolerated but less potent
2. Amiloride (5-10 mg daily)
3. Doxazosin (alpha-blocker, 1-8 mg daily)
4. Clonidine (central alpha-agonist, 0.1-0.3 mg twice daily)

Rationale for Spironolactone

Spironolactone is particularly effective in resistant hypertension for several reasons:

• The 2024 ESC guidelines specifically recommend adding low-dose spironolactone to existing treatment for resistant hypertension 1
• The 2018 AHA statement on resistant hypertension places spironolactone as the preferred fourth-line agent 1
• Studies show significant BP reductions (25/12 mmHg) when added to regimens already containing an ARB, CCB, and diuretic 2
• Effective regardless of plasma aldosterone or renin levels 1

Monitoring and Follow-up

• Check serum potassium and renal function within 1-2 weeks after starting spironolactone
• Avoid spironolactone if serum potassium >5.0 mEq/L or eGFR <45 ml/min/1.73m² 1
• Target BP should be <130/80 mmHg if tolerated 1
• Follow-up BP assessment within 4-6 weeks

Important Considerations and Cautions

• Hyperkalemia risk: Higher risk when combining spironolactone with ARBs like valsartan
• Sexual side effects: Gynecomastia and erectile dysfunction may occur with spironolactone; consider eplerenone if these develop
• Renal function: Monitor closely, especially in patients with reduced eGFR
• Dosing: Start low (25 mg) and titrate based on response and tolerability

If BP Remains Uncontrolled

If blood pressure remains uncontrolled despite the addition of spironolactone:

1. Consider switching hydrochlorothiazide to a thiazide-like diuretic (chlorthalidone or indapamide) 1
2. Consider referral to a hypertension specialist
3. Evaluate for device-based interventions like renal denervation in specialized centers 1

The evidence strongly supports adding spironolactone as the most effective next step for this patient with resistant hypertension, with expected significant improvements in blood pressure control and reduction in cardiovascular risk.