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 a fourth-line agent in appropriate patients. 1

Definition and Confirmation of Resistant Hypertension

Resistant hypertension is defined as:

• Blood pressure >140/90 mmHg despite treatment with ≥3 antihypertensive medications at optimal doses, including a diuretic 1
• Or blood pressure requiring ≥4 antihypertensive drugs to achieve control 2

Step 1: Exclude Pseudoresistance

Before confirming true resistant hypertension, rule out:

• Poor BP measurement technique
• White coat effect (confirm with 24-hour ambulatory BP monitoring)
• Medication nonadherence
• Suboptimal medication choices or dosing 1, 2

Approximately 50% of patients diagnosed with resistant hypertension have pseudoresistance rather than true resistant hypertension. 1

Step 2: Screen 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
• Strong clinical clues suggesting secondary cause 1, 2

Common secondary causes include:

• Primary aldosteronism (present in ~20% of resistant hypertension cases)
• Renal parenchymal disease
• Renovascular hypertension
• Chronic sleep apnea
• Substance/drug-induced hypertension 1, 2

Basic screening should include:

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

Step 3: Optimize Current Treatment Regimen

Lifestyle Modifications

• Sodium restriction (<2400 mg/day)
• Weight loss if indicated
• Regular physical activity
• DASH diet
• Limited alcohol intake 1, 2

Optimize Medication Regimen

1. Ensure optimal three-drug combination:

   • ACE inhibitor or ARB
   • Long-acting calcium channel blocker
   • Thiazide-like diuretic 1, 2

2. Optimize diuretic therapy:

   • Use thiazide-like diuretics (chlorthalidone or indapamide) rather than thiazide diuretics 1
   • Use loop diuretics for eGFR <30 ml/min/1.73m² or clinical volume overload 1, 2
   • Consider replacing hydrochlorothiazide with chlorthalidone (more effective long-acting thiazide-like diuretic) 2, 3

Step 4: Add Fourth-Line Agent

Add spironolactone as the fourth-line agent in patients whose:

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

Starting dose of spironolactone is typically 25 mg daily, which can be titrated up to 50 mg daily 2

Alternatives if Spironolactone is Contraindicated or Not Tolerated:

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

Step 5: Further Treatment Options if BP Remains Uncontrolled

If BP remains uncontrolled despite the above measures, consider:

1. Add beta-blocker (if heart rate ≥70 beats/min) 1
2. Add hydralazine and titrate upward to maximum dose 1
3. Consider minoxidil if hydralazine is ineffective 1
4. Consider referral to a specialist center with expertise in resistant hypertension 1

Special Considerations

Ethnic Differences

• In Black patients, initial antihypertensive treatment should include a diuretic or a calcium channel blocker 1, 2

Monitoring and Follow-up

• Use ambulatory or home BP monitoring to confirm diagnosis and monitor treatment response 1, 2
• Monitor serum creatinine/eGFR and potassium levels at least annually, especially when using ACE inhibitors, ARBs, or diuretics 1
• More frequent monitoring is needed when adding spironolactone, particularly in patients with CKD or diabetes 2

Common Pitfalls to Avoid

• Therapeutic inertia (not intensifying treatment despite persistently elevated BP)
• Inadequate diuretic therapy
• Overlooking medication adherence
• Neglecting secondary causes
• Inappropriate medication timing
• Overlooking interfering substances 2

Resistant hypertension should be managed in specialist centers with sufficient expertise and resources necessary to diagnose and treat this condition when initial approaches fail 1.