What is the best treatment for resistant hypertension?

Best Treatment for Resistant Hypertension

The most effective treatment for resistant hypertension is adding spironolactone as a fourth-line agent to an optimized three-drug regimen that includes a long-acting calcium channel blocker, a renin-angiotensin system blocker, and a thiazide-like diuretic. 1, 2, 3

Definition and Diagnosis

• Resistant hypertension is defined as blood pressure that remains above target (>130/80 mmHg) despite concurrent use of at least three antihypertensive agents of different classes at maximal or maximally tolerated doses, or BP control requiring four or more drugs 4, 2
• True resistant hypertension must be distinguished from pseudoresistance by:
  • Confirming with 24-hour ambulatory blood pressure monitoring to exclude white-coat effect 1, 2
  • Assessing medication adherence, which accounts for approximately 50% of apparent treatment resistance 4, 2
  • Ruling out interfering substances (NSAIDs, oral contraceptives, stimulants) 4, 2

Treatment Algorithm

Step 1: Optimize Lifestyle Modifications

• Implement dietary sodium restriction to less than 2400 mg/day 1, 2
• Encourage weight loss for overweight/obese patients 1, 2
• Increase physical activity with structured exercise program 4
• Limit alcohol consumption (≤2 drinks/day for men, ≤1 drink/day for women) 4
• Consider DASH diet to facilitate achieving desirable weight 4

Step 2: Optimize Current Medication Regimen

• Ensure optimal dosing of current medications 2
• Consider switching to a thiazide-like diuretic (chlorthalidone) if patient is on hydrochlorothiazide 2
• Simplify regimen when possible to improve adherence 2
• Address volume overload with appropriate diuretic therapy 2

Step 3: Add Fourth-Line Agent

• Add spironolactone 25mg daily as the fourth agent - this has demonstrated superior efficacy in resistant hypertension 1, 2, 3
• Monitor serum potassium and renal function 1-2 weeks after initiating spironolactone, particularly with existing RAS blockade 1, 2
• If spironolactone is not tolerated, consider eplerenone as an alternative 2, 5
• If mineralocorticoid receptor antagonists are contraindicated, add either:
  • Additional diuretic therapy
  • Beta-blocker
  • Alpha-blocker 2

Evaluation for Secondary Causes

• Screen all patients with resistant hypertension for:
  • Primary aldosteronism (even with normal potassium levels) 4, 1
  • Obstructive sleep apnea 4
  • Chronic kidney disease 4, 2
  • Renal artery stenosis 1
  • Other endocrine disorders 1

Special Considerations

• In patients with eGFR between 30-50 mL/min/1.73m², consider initiating spironolactone at 25mg every other day due to hyperkalemia risk 5
• For Black patients, ensure regimen includes a diuretic or calcium channel blocker 2
• In patients with heart failure, include ACE inhibitor/ARB, beta-blocker, and mineralocorticoid receptor antagonist 2, 5
• For severe cases not responding to optimal medical therapy, consider referral for device-based approaches such as renal denervation, though evidence for long-term outcomes remains limited 3, 6

Monitoring

• Assess blood pressure response within 2-4 weeks of medication adjustment 1
• Monitor serum potassium and renal function regularly, especially after initiating spironolactone 1, 5
• Consider home blood pressure monitoring to guide medication titration and improve adherence 4

Common Pitfalls

• Failing to confirm true resistant hypertension before escalating therapy 4, 2
• Inadequate diuretic therapy leading to volume overload 2
• Not screening for secondary causes, particularly primary aldosteronism 4, 1
• Overlooking medication non-adherence as a cause of apparent resistance 4, 2
• Using suboptimal medication combinations or inadequate doses 2