What is the initial approach to managing resistant hypertension?

Initial Approach to Managing Resistant Hypertension

The initial approach to managing resistant hypertension should first exclude pseudoresistance, then optimize the current treatment regimen including lifestyle modifications and diuretic-based therapy, followed by adding spironolactone as the fourth-line agent in appropriate patients. 1

Definition and Prevalence

Resistant hypertension is defined as:

• Blood pressure >140/90 mmHg despite treatment with three or more antihypertensive medications at optimal (or maximally tolerated) doses
• One of these medications must be a diuretic
• Affects approximately 10% of hypertensive individuals
• Associated with increased risk of coronary artery disease, heart failure, stroke, end-stage renal disease, and all-cause mortality 1

Step 1: Rule Out Pseudoresistance

Before diagnosing true resistant hypertension, exclude:

• Poor BP measurement technique: Ensure proper cuff size and measurement procedure
• White coat effect: Confirm with ambulatory or home BP monitoring
• Medication nonadherence: Assess barriers to adherence (cost, side effects)
• Suboptimal medication choices/combinations: Review current regimen
• Substance/drug-induced hypertension: NSAIDs, stimulants, decongestants, alcohol, illicit drugs 1, 2

Step 2: Screen for Secondary Causes

Consider screening for secondary hypertension in patients with resistant hypertension, particularly:

• Renal parenchymal disease
• Renovascular hypertension
• Primary aldosteronism
• Obstructive sleep apnea
• Substance/drug-induced hypertension 1, 3

Basic screening should include:

• Thorough history and physical examination
• Basic blood biochemistry (sodium, potassium, eGFR, TSH)
• Urinalysis 1

Step 3: Optimize Current Treatment Regimen

1. Lifestyle modifications:

   • Sodium restriction (particularly important in resistant hypertension)
   • Weight loss if indicated
   • Regular physical activity
   • Limited alcohol consumption 1, 4

2. Optimize diuretic therapy:

   • Use thiazide-like diuretics (chlorthalidone, indapamide) rather than thiazide diuretics
   • Consider loop diuretics for eGFR <30 ml/min/1.73m² or clinical volume overload
   • Ensure appropriate dosing (e.g., chlorthalidone 25-50 mg daily) 1, 5

3. Review and optimize other antihypertensive medications:

   • Ensure optimal dosing of all medications
   • Consider single-pill combinations to improve adherence
   • Ensure appropriate timing of medication administration 1

Step 4: Add Fourth-Line Agent

Add spironolactone as the fourth-line agent if:

• Serum potassium <4.5 mmol/L
• eGFR >45 ml/min/1.73m² 1

Initial dosing:

• Start at 25 mg daily
• Can be titrated up to 50 mg daily as needed and tolerated 6

If spironolactone is contraindicated or not tolerated, consider alternatives:

• Eplerenone
• Amiloride
• Doxazosin
• Clonidine
• Beta-blockers
• Any available antihypertensive class not already in use 1

Monitoring and Follow-up

• Monitor serum potassium and renal function regularly, especially when using spironolactone with ACE inhibitors or ARBs 1, 6
• Use ambulatory BP monitoring to confirm BP control and guide therapy adjustments 7
• Consider referral to a hypertension specialist for patients with persistent uncontrolled BP despite optimization of therapy 1

Special Considerations

• Diabetes: Consider mineralocorticoid receptor antagonists for patients not meeting BP targets on three classes of medications (including a diuretic) 1
• Chronic kidney disease: Use loop diuretics instead of thiazides when eGFR <30 ml/min/1.73m² 1
• Black patients: Initial therapy should include a diuretic or CCB, either in combination or with a RAS blocker 1

Pitfalls to Avoid

• Failing to confirm true resistant hypertension before escalating therapy
• Not considering secondary causes of hypertension
• Inadequate diuretic therapy (inappropriate type or dose)
• Adding a fourth agent before optimizing the first three
• Inadequate monitoring of electrolytes and renal function when using spironolactone
• Not referring complex cases to specialists when appropriate 1, 4