What should I do for a patient with uncontrolled hypertension, currently on hydrochlorothiazide (HCTZ) 12.5mg and amlodipine 10mg, with a blood pressure of 160/92?

Management of Uncontrolled Hypertension on Current Therapy

For a patient with uncontrolled hypertension (BP 160/92) on HCTZ 12.5mg and amlodipine 10mg, you should add an ACE inhibitor or ARB as the next step in therapy.

Assessment of Current Therapy

The patient's current regimen includes:

• Amlodipine 10mg (maximum dose) 1
• HCTZ 12.5mg (starting dose)

This two-drug combination has proven insufficient to control blood pressure, which at 160/92 mmHg indicates Stage 2 hypertension requiring more aggressive management.

Recommended Treatment Algorithm

1. First step: Add an ACE inhibitor or ARB to the current regimen

   • This creates a triple-drug regimen that includes a calcium channel blocker (amlodipine), a diuretic (HCTZ), and a renin-angiotensin system (RAS) blocker
   • The combination of these three classes has shown superior efficacy in managing resistant hypertension 2

2. If BP remains uncontrolled after adding an ACE inhibitor/ARB:

   • Consider replacing HCTZ with chlorthalidone (starting at 12.5mg)
   • Chlorthalidone has been shown to provide greater 24-hour BP reduction compared to HCTZ at equivalent doses 3

3. If still uncontrolled:

   • Add a mineralocorticoid receptor antagonist (spironolactone 25mg) as fourth-line therapy 4

Rationale for Adding an ACE Inhibitor/ARB

1. Evidence-based approach: Guidelines recommend a triple-drug regimen including a RAS blocker, calcium channel blocker, and diuretic as optimal therapy for resistant hypertension 2

2. Complementary mechanisms: ACE inhibitors/ARBs work synergistically with calcium channel blockers and diuretics by targeting different pathways of blood pressure regulation 5

3. Outcome benefits: In patients with hypertension, RAS inhibitors have demonstrated unique advantages for reducing cardiovascular outcomes 2

Optimization of Current Therapy

While adding a new agent:

1. Consider diuretic optimization:

   • The current HCTZ dose (12.5mg) is the starting dose
   • If adding an ACE inhibitor/ARB doesn't achieve target BP, consider increasing HCTZ to 25mg or switching to chlorthalidone 2
   • For patients with chronic kidney disease (eGFR <30 mL/min), consider switching to a loop diuretic 2

2. Ensure proper administration:

   • Amlodipine is already at maximum dose (10mg) 1
   • Consider administering at least one antihypertensive medication at bedtime, which has been shown to reduce cardiovascular events 2

Important Considerations

• Medication adherence: Confirm the patient is taking medications as prescribed, as non-adherence is a common cause of apparent resistant hypertension 2

• Lifestyle modifications: Reinforce dietary salt restriction (<2,300 mg/day), weight loss if applicable, regular physical activity, and limited alcohol intake 2, 5

• Rule out secondary causes: If BP remains uncontrolled despite triple therapy, consider evaluation for secondary hypertension (sleep apnea, primary aldosteronism, chronic kidney disease, etc.) 2

• Monitoring: After adding a new medication, reassess BP within 2-4 weeks to evaluate efficacy and adjust therapy as needed 5

Common Pitfalls to Avoid

• Therapeutic inertia: Delaying intensification of therapy despite uncontrolled BP increases risk of cardiovascular events

• Inappropriate combinations: Avoid combining two RAS blockers (ACE inhibitor + ARB) as this increases adverse effects without significant BP benefit 5

• Inadequate diuretic therapy: Resistant hypertension often involves volume expansion that requires effective diuretic therapy 2

• Overlooking interfering substances: NSAIDs can reduce the effectiveness of antihypertensive medications, particularly diuretics 6