What is the treatment approach for patients with resistant hypertension?

Treatment Approach for Resistant Hypertension

For patients with resistant hypertension, adding spironolactone as a fourth-line agent is the most effective approach when serum potassium is <4.5 mmol/L and eGFR is >45 ml/min/1.73m². 1, 2

Diagnosis and Confirmation

• Resistant hypertension is defined as seated office BP >140/90 mm Hg despite treatment with three or more antihypertensive medications at optimal doses including a diuretic 1
• Before diagnosing true resistant hypertension, exclude pseudoresistance causes:
  • Poor BP measurement technique
  • White coat effect (confirm with 24-hour ambulatory BP monitoring)
  • Medication nonadherence (accounts for ~50% of apparent resistance)
  • Suboptimal medication choices 1, 2
• Screen for secondary causes of hypertension, particularly in patients with:
  • Early onset hypertension (<30 years)
  • Sudden deterioration in BP control
  • Hypertensive urgency or emergency 1

Treatment Algorithm

Step 1: Optimize Current Regimen

• Ensure optimal doses of existing medications, particularly diuretics 1
• Use thiazide-like diuretics (e.g., chlorthalidone) rather than thiazide diuretics 1, 3
• Switch to loop diuretics if eGFR <30 ml/min/1.73m² or clinical volume overload 1, 3

Step 2: Lifestyle Modifications

• Implement dietary salt restriction (ideally <100 mEq sodium/24-hour) 1
• Encourage weight loss - a 10-kg weight loss can reduce systolic BP by ~6.0 mm Hg 1
• Limit alcohol intake to no more than 2 drinks/day for men and 1 drink/day for women 1
• Increase physical activity (minimum 30 minutes on most days) 1

Step 3: Add Fourth-Line Agent

• Add spironolactone 25mg daily as the fourth agent when:
  • Serum potassium is <4.5 mmol/L
  • eGFR is >45 ml/min/1.73m² 1, 2, 4
• If spironolactone is contraindicated or not tolerated, alternatives include:
  • Amiloride
  • Eplerenone
  • Doxazosin
  • Clonidine
  • Beta-blockers 1, 5

Step 4: Monitor and Adjust

• Check serum potassium and renal function 1-2 weeks after initiating spironolactone 5
• Monitor BP response within 2-4 weeks of medication adjustment 5
• Consider referral to specialist centers with expertise in managing resistant hypertension if BP remains uncontrolled 1

Special Considerations

Medication Adherence

• Simplify medication regimen using long-acting combination products 1
• Consider more frequent clinic visits and home BP monitoring to enhance adherence 1
• A multidisciplinary approach including nurse case managers, pharmacists, and nutritionists can improve outcomes 1, 2

Secondary Causes

• Common secondary causes include:
  • Renal parenchymal disease
  • Renovascular hypertension
  • Primary aldosteronism
  • Obstructive sleep apnea
  • Substance/drug-induced hypertension 1, 6
• Treat underlying secondary causes when identified 1

Common Pitfalls and Caveats

• Volume overload due to insufficient diuretic therapy is a common cause of treatment failure 2, 3
• Medications like NSAIDs, certain antidepressants, and stimulants can interfere with BP control 2, 7
• Pseudoresistance is common (approximately 50% of apparent resistant hypertension cases) and must be excluded before intensifying therapy 1, 8
• White coat effect should be excluded using 24-hour ambulatory BP monitoring 2, 8
• High sodium intake significantly contributes to treatment resistance 1, 2