What is the best approach to managing resistant hypertension?

Management of Resistant Hypertension

The best approach to managing resistant hypertension is to first exclude pseudoresistance, then optimize lifestyle modifications, ensure appropriate diuretic-based therapy, and add spironolactone as a fourth-line agent in suitable patients. 1, 2

Confirming True Resistant Hypertension

• Resistant hypertension is defined as seated office BP >140/90 mm Hg in a patient treated with three or more antihypertensive medications at optimal doses including a diuretic 1
• Exclude pseudoresistance causes before proceeding with further management:
  • Poor BP measurement technique
  • White coat effect (confirm with 24-hour ambulatory BP monitoring)
  • Medication nonadherence
  • Suboptimal antihypertensive therapy choices 1, 2
• Approximately 50% of patients diagnosed with resistant hypertension have pseudoresistance rather than true resistant hypertension 1
• Review all medications and substances that may interfere with BP control (NSAIDs, oral contraceptives, decongestants, stimulants) 2

Screening for Secondary Causes

• Consider screening for secondary hypertension in patients with:
  • Early onset hypertension (<30 years of age)
  • Resistant hypertension
  • Sudden deterioration in BP control
  • Hypertensive urgency/emergency 1
• Common secondary causes include:
  • Renal parenchymal disease
  • Renovascular hypertension
  • Primary aldosteronism
  • Obstructive sleep apnea
  • Substance/drug-induced hypertension 1, 2
• Basic screening should include thorough history, physical examination, basic blood biochemistry (sodium, potassium, eGFR, TSH), and urinalysis 1
• Further investigations should be carefully chosen based on clinical suspicion 1

Optimizing Lifestyle Modifications

• Dietary salt restriction to less than 1500 mg/day can reduce systolic and diastolic BP by 5-10 and 2-6 mm Hg, respectively 1, 2
• Weight loss of 10 kg is associated with an average 6.0 mm Hg reduction in systolic and 4.6 mm Hg reduction in diastolic BP 1
• Regular aerobic exercise for at least 30 minutes on most days of the week can produce average reductions of 4 mm Hg in systolic and 3 mm Hg in diastolic BP 1
• Limit alcohol intake to no more than 2 drinks per day for men and 1 drink per day for women 1
• Adopt a DASH diet (high in fruits, vegetables, low-fat dairy products, potassium, magnesium, and calcium; low in saturated fats) 1, 2

Pharmacological Management Algorithm

1. Optimize current regimen:

   • Ensure maximal tolerated doses of three first-line agents including a diuretic 1
   • Use thiazide-like diuretics (e.g., chlorthalidone) rather than thiazide diuretics 1
   • Consider loop diuretics for patients with eGFR <30 ml/min/1.73m² or clinical volume overload 1

2. Add fourth-line agent:

   • Spironolactone is the preferred fourth-line agent for patients with serum potassium <4.5 mmol/L and eGFR >45 ml/min/1.73m² 1, 2, 3
   • Spironolactone is indicated for add-on therapy for hypertension not adequately controlled on other agents 4
   • Monitor serum potassium and renal function when using spironolactone, especially with reduced renal function 2

3. Alternative fourth-line agents if spironolactone is contraindicated or not tolerated:

   • Amiloride
   • Doxazosin
   • Eplerenone
   • Clonidine
   • Beta-blockers 1, 3

4. Consider combination therapy including:

   • Long-acting calcium channel blocker (e.g., amlodipine) 5, 3
   • Angiotensin-converting enzyme inhibitor (e.g., lisinopril) or angiotensin receptor blocker 6, 3
   • Diuretic at maximal tolerated dose 3

Special Considerations

• Patients with CKD have a higher prevalence of resistant hypertension (40% in the CRIC Study) 1
• For patients with CKD, consider using modalities that do not involve iodinated contrast when imaging for renal artery stenosis 1
• Treatment of obstructive sleep apnea with CPAP may improve BP control, though benefits in intervention trials have been variable 1
• Simplify medication regimens when possible to improve adherence, including use of long-acting combination products to reduce pill burden 1, 2
• Involve patients in their care through home BP monitoring and maintenance of BP diaries 1

Referral Recommendations

• Resistant hypertension should be managed in specialist centers with sufficient expertise and resources 1
• Consider referral to a specialist (nephrologist, cardiologist, endocrinologist) if BP remains uncontrolled despite optimal therapy with 4+ medications 1, 2
• Refer for further investigation and management of suspected secondary hypertension to a specialist center 1

Common Pitfalls to Avoid

• Failing to confirm true resistant hypertension before escalating therapy 1, 2
• Not screening for secondary causes, especially in younger patients or those with sudden BP deterioration 1
• Inadequate dosing, lack of using long-acting diuretics, and suboptimal combinations (observed in nearly half of patients with resistant hypertension) 7
• Overlooking medication nonadherence, which accounts for approximately 50% of apparent treatment-resistant hypertension 1
• Neglecting the importance of sodium restriction in the management plan 1