What is the appropriate workup and treatment for a patient with resistant hypertension?

Resistant Hypertension Workup and Treatment

Resistant hypertension requires a systematic approach beginning with confirmation of true resistance, screening for secondary causes, and optimization of pharmacological therapy with spironolactone as the preferred fourth-line agent. 1

Confirming True Resistant Hypertension

• Resistant hypertension is defined as BP >140/90 mmHg despite treatment with three or more antihypertensive medications at optimal doses, including a diuretic 1
• Exclude pseudoresistance before confirming diagnosis:
  • Verify proper BP measurement technique (patient seated quietly for 5 minutes, correct cuff size, arm at heart level, average of at least 2 readings) 1
  • Perform 24-hour ambulatory BP monitoring or home BP monitoring to exclude white coat effect 1
  • Assess medication adherence through direct questioning about barriers (cost, side effects, dosing inconvenience) 1, 2
  • Review all medications and substances that may interfere with BP control (NSAIDs, decongestants, oral contraceptives) 2

Screening for Secondary Causes

• Secondary hypertension is present in up to 50% of patients with resistant hypertension 1
• Key secondary causes to screen for:
  • Primary aldosteronism: Check aldosterone-to-renin ratio, especially in patients with hypokalemia 1
  • Obstructive sleep apnea: Screen for symptoms (daytime sleepiness, snoring, witnessed apnea) 1, 2
  • Chronic kidney disease: Assess eGFR and urinalysis 1, 2
  • Renal artery stenosis: Consider in patients with atherosclerotic disease or worsening renal function 1
  • Pheochromocytoma: Consider in patients with episodic hypertension, palpitations, diaphoresis 1
  • Cushing's syndrome: Look for characteristic physical features (moon facies, central obesity, striae) 1

Optimizing Pharmacological Treatment

• Ensure optimal diuretic therapy:
  • Use thiazide-like diuretics (chlorthalidone) rather than thiazide diuretics 1, 3
  • Switch to loop diuretics if eGFR <30 ml/min/1.73m² or clinical volume overload 1, 2
• Combine agents with different mechanisms of action:
  • RAS blocker (ACE inhibitor or ARB) 4
  • Long-acting calcium channel blocker 5
  • Diuretic at optimal dose 3
• Add spironolactone 25 mg daily as the preferred fourth-line agent in patients with serum potassium <4.5 mmol/L and eGFR >45 ml/min/1.73m² 1, 6, 5
• Alternative fourth-line agents if spironolactone is contraindicated or not tolerated:
  • Amiloride 1, 5
  • Doxazosin 1, 7
  • Eplerenone 6, 5
  • Clonidine 1, 8
  • Beta-blockers 1, 7

Lifestyle Modifications

• Sodium restriction (<1500 mg/day) 2, 9
• Weight loss if overweight/obese 2, 8
• Regular physical activity 2, 9
• Moderation of alcohol intake 2, 8
• DASH diet with increased potassium intake 2, 9

Referral to Specialist

• Refer to hypertension specialist if:
  • BP remains uncontrolled after 6 months of treatment 1
  • Secondary cause of hypertension is suspected 1, 2
  • Patient is young (<30 years) with resistant hypertension 1, 2
  • Complex medication regimen is needed (≥4 medications) 1, 10

Common Pitfalls and Caveats

• Failure to confirm true resistance by excluding pseudoresistance is a common mistake 1, 7
• Inadequate diuretic therapy is frequently observed in resistant hypertension 9, 8
• Suboptimal dosing or inappropriate combinations account for nearly half of resistant hypertension cases 8, 7
• Overlooking primary aldosteronism, which is present in up to 12% of patients with severe hypertension 1, 5
• Not considering spironolactone as fourth-line therapy despite strong evidence for its efficacy 1, 5
• Failing to monitor serum potassium and renal function when using spironolactone, especially with reduced eGFR 2, 6