What is the treatment for Resistant Arterial Hypertension (RAS HT)?

Treatment for Resistant Arterial Hypertension (RAS HT)

The most effective treatment for resistant hypertension requires a multi-drug regimen including a long-acting thiazide-like diuretic, a RAS blocker (ACE inhibitor or ARB), a calcium channel blocker, and spironolactone as a fourth agent, along with intensive lifestyle modifications. 1

Definition and Diagnosis

Resistant hypertension is defined as:

• Blood pressure remaining above goal (>140/90 mmHg) despite concurrent use of 3 antihypertensive agents of different classes at optimal doses, including a diuretic 2, 1
• True resistant hypertension must be distinguished from pseudoresistance (white coat effect, poor medication adherence, improper BP measurement) 1

Treatment Algorithm

Step 1: Optimize the Initial 3-Drug Regimen

• First-line combination: 1
  • Long-acting thiazide-like diuretic (chlorthalidone preferred over hydrochlorothiazide)
  • RAS blocker (ACE inhibitor like lisinopril or ARB)
  • Long-acting calcium channel blocker (amlodipine)
• Special considerations:
  • For eGFR <30 mL/min/1.73m², substitute loop diuretic for thiazide 1
  • Ensure medications are at maximum tolerated doses 2, 1

Step 2: Add Fourth Agent

• Preferred fourth agent: Spironolactone 12.5-25 mg daily 1
  • Most effective in patients with serum potassium <4.5 mmol/L and eGFR >45 ml/min/1.73m² 1
  • Monitor serum potassium and renal function closely 1
• Alternatives if spironolactone is contraindicated or not tolerated: 1
  • Eplerenone (alternative mineralocorticoid receptor antagonist)
  • Amiloride (potassium-sparing diuretic)
  • Doxazosin (alpha-blocker)

Step 3: Further Additions if Needed

• If heart rate ≥70 beats/min, add β-blocker or combined α-β-blocker 1
• Consider central α-agonist (clonidine) if β-blocker is contraindicated 1
• Add hydralazine (starting at 25 mg three times daily) and titrate upward 1
• Consider minoxidil as a last resort for truly refractory cases 1

Essential Lifestyle Modifications

• Sodium restriction (<2400 mg/day) 2, 1
• Weight loss if overweight/obese (10-kg weight loss can reduce SBP by 6 mmHg) 2, 1
• Regular physical activity 1
• DASH diet (high in fruits, vegetables, low-fat dairy; low in saturated fat) 1
• Limited alcohol intake 2, 1

Addressing Secondary Causes

Always evaluate for secondary causes of resistant hypertension: 2, 1

• Primary aldosteronism (screen with plasma aldosterone/renin ratio)
• Obstructive sleep apnea (common in resistant hypertension)
• Renal artery stenosis (especially in young women or older patients with atherosclerotic risk)
• Chronic kidney disease
• Pheochromocytoma (rare)

Monitoring and Follow-up

• Use ambulatory or home BP monitoring to confirm diagnosis and treatment response 1
• Monitor serum creatinine/eGFR and potassium levels, especially after adding spironolactone 1
• Consider referral to hypertension specialist if BP remains uncontrolled despite optimized therapy 2, 1

Common Pitfalls to Avoid

• Failing to confirm true resistant hypertension (vs. pseudoresistance) 1
• Inadequate diuretic therapy 2, 1
• Overlooking medication adherence issues 2, 1
• Neglecting to screen for secondary causes 2, 1
• Inappropriate medication timing 1
• Overlooking interfering substances (NSAIDs, certain supplements) 2, 3

By following this structured approach to resistant hypertension management, blood pressure control can be achieved in the majority of patients, reducing cardiovascular morbidity and mortality.