What is the best approach to managing resistant hypertension?

Management of Resistant Hypertension

The most effective approach to managing resistant hypertension is a stepwise process that begins with confirming true resistance, excluding pseudoresistance, optimizing the current medication regimen with addition of spironolactone as fourth-line therapy, and addressing secondary causes. 1, 2

Confirming True Resistant Hypertension

• Resistant hypertension is defined as BP >140/90 mmHg despite treatment with three or more optimally dosed antihypertensive medications including a diuretic, or controlled BP requiring four or more medications 1
• Exclude pseudoresistance before confirming diagnosis:
  • Poor BP measurement technique (use proper cuff size and positioning) 1, 2
  • White coat effect (perform 24-hour ambulatory BP monitoring) 2
  • Medication nonadherence (verify through direct questioning or drug level testing) 2
  • Suboptimal medication choices or dosing 1
• Identify and discontinue substances that may interfere with BP control:
  • NSAIDs, oral contraceptives, decongestants, stimulants, alcohol, and high sodium intake 1, 2

Optimizing Current Treatment Regimen

1. Lifestyle modifications (essential for all patients):

   • Dietary sodium restriction (<1500 mg/day) - can reduce systolic BP by 5-10 mmHg 1
   • Weight loss if overweight/obese - 10 kg weight loss associated with 6.0 mmHg systolic BP reduction 1
   • Regular physical activity (minimum 30 minutes most days) 1
   • Moderation of alcohol intake (≤2 drinks/day for men, ≤1 drink/day for women) 1
   • High-fiber, low-fat diet (DASH diet) 1

2. Optimize diuretic therapy:

   • Use thiazide-like diuretics (chlorthalidone) rather than thiazide diuretics 1
   • Consider loop diuretics for patients with eGFR <30 ml/min/1.73m² or clinical volume overload 1
   • Ensure maximal tolerated doses 1

3. Optimize three-drug regimen:

   • Include a long-acting calcium channel blocker (e.g., amlodipine) 3, 4
   • Include a renin-angiotensin system blocker (ACE inhibitor like lisinopril or ARB) 5, 4
   • Include a diuretic at optimal dose 1, 4
   • Simplify regimen when possible to improve adherence (use combination pills) 1

4. Add fourth-line agent:

   • Add spironolactone 25 mg daily as the preferred fourth-line agent when serum potassium <4.5 mmol/L and eGFR >45 ml/min/1.73m² 1, 6
   • Monitor potassium and renal function when using spironolactone, especially with reduced kidney function 2
   • Alternative fourth-line agents if spironolactone is contraindicated or not tolerated: amiloride, doxazosin, eplerenone, clonidine, or beta-blockers 1, 4

Screening for Secondary Causes

• Consider screening for secondary hypertension in all patients with resistant hypertension 1
• Common secondary causes to evaluate:
  • Primary aldosteronism (screen with aldosterone/renin ratio) 1
  • Chronic kidney disease (assess with serum creatinine, eGFR, urinalysis) 1
  • Renovascular disease (consider renal artery imaging in high-risk patients) 1, 2
  • Obstructive sleep apnea (screen with Berlin Questionnaire or Epworth Sleepiness Score) 1, 2
  • Pheochromocytoma (measure 24-hour urinary metanephrines or plasma metanephrines if suspected) 1
• Note: Treatment of obstructive sleep apnea with CPAP may not substantially reduce BP but has other benefits 1

When to Refer to Specialists

• Refer patients with resistant hypertension to specialist centers with sufficient expertise and resources 1
• Consider referral when:
  • BP remains uncontrolled despite optimization of 4+ medication regimen 2
  • Strong suspicion of secondary hypertension 1
  • Early onset hypertension (<30 years of age) 1, 2
  • Sudden deterioration in previously controlled BP 1

Monitoring and Follow-up

• Regular monitoring of BP control with home BP monitoring in addition to office measurements 2
• Monitor serum potassium and renal function when using spironolactone 2
• Reassess for secondary causes if BP control deteriorates after initial stabilization 2

Common Pitfalls to Avoid

• Failing to confirm true resistant hypertension before escalating therapy 1
• Overlooking medication nonadherence, which accounts for approximately 50% of apparent treatment resistance 1
• Using inadequate doses of diuretics, especially in patients with volume overload 1
• Not considering secondary causes, particularly in young patients or those with sudden BP changes 1
• Using medications with similar mechanisms of action rather than complementary agents 1