What is the next step in managing a 65-year-old male with resistant hypertension who is currently taking amlodipine (calcium channel blocker) 10 mg, spironolactone (aldosterone antagonist) 25 mg, and losartan (angiotensin II receptor antagonist) 100 mg?

Management of Resistant Hypertension in a 65-Year-Old Male

For a 65-year-old male with resistant hypertension currently on amlodipine 10 mg, spironolactone 25 mg, and losartan 100 mg, the next step in management should be to add a thiazide-like diuretic such as chlorthalidone or indapamide. 1

Current Medication Assessment

The patient is currently on:

• Amlodipine 10 mg (calcium channel blocker) at maximum dose
• Losartan 100 mg (angiotensin receptor blocker) at maximum dose
• Spironolactone 25 mg (mineralocorticoid receptor antagonist)

This regimen includes two of the three first-line agents recommended for hypertension management (ARB and CCB), plus spironolactone as a fourth-line agent. However, the patient is missing an appropriate diuretic in the regimen, which is a critical component for managing resistant hypertension.

Next Step in Management

Add a Thiazide-like Diuretic

• Add chlorthalidone (12.5-25 mg daily) or indapamide (1.25-2.5 mg daily) 1
• Thiazide-like diuretics are more effective than traditional thiazides like hydrochlorothiazide, especially in resistant hypertension
• These maintain efficacy down to estimated glomerular filtration rates (eGFRs) of 30 mL⋅min−1⋅1.73 m−2 1

Rationale for Adding a Thiazide-like Diuretic

1. Complete the Core Regimen: The American Heart Association defines resistant hypertension as BP remaining above target despite treatment with 3 antihypertensive agents of different classes, including a diuretic 1, 2

2. Evidence-Based Approach: The 2018 AHA Scientific Statement on resistant hypertension specifically recommends substituting an optimally dosed thiazide-like diuretic as Step 2 in management 1

3. Synergistic Mechanism: Adding a thiazide-like diuretic will complement the existing medications by:

   • Promoting sodium and water excretion
   • Reducing intravascular volume
   • Working synergistically with the RAS blockade from losartan 1, 3

Monitoring Recommendations

• Check electrolytes and renal function 2-4 weeks after adding the thiazide-like diuretic 3
• Monitor for hyponatremia, hypokalemia, and worsening renal function
• Reassess BP control within 4 weeks of medication adjustment 1
• Target BP should be <130/80 mmHg for this 65-year-old patient 3

Alternative Options if BP Remains Uncontrolled

If BP remains uncontrolled after adding a thiazide-like diuretic:

1. Increase Spironolactone Dose: Consider titrating spironolactone from 25 mg to 50 mg daily if potassium and renal function permit 4

2. Add Beta-Blocker: If heart rate is ≥70 bpm, consider adding metoprolol succinate or bisoprolol 1

3. Add Alpha-Blocker: Consider doxazosin as an alternative if beta-blockers are contraindicated 1

Important Considerations

• Check Adherence: Ensure patient is taking all medications as prescribed 1, 2
• Lifestyle Modifications: Reinforce sodium restriction (<2.3g/day), regular physical activity, weight management, and alcohol limitation 3
• Exclude Secondary Causes: Consider screening for obstructive sleep apnea, primary aldosteronism, renal artery stenosis, or other secondary causes if BP remains difficult to control 1
• Monitor for Adverse Effects: Watch for hyperkalemia with the combination of spironolactone and losartan, especially if renal function declines 4

Adding a thiazide-like diuretic represents the most evidence-based next step in management for this patient with resistant hypertension, completing the recommended core regimen while maximizing the synergistic effects of the different antihypertensive classes.