What is the approach to managing resistant hypertension?

Approach to Resistant Hypertension

Confirm True Resistant Hypertension First

Before intensifying therapy, perform 24-hour ambulatory blood pressure monitoring to exclude pseudoresistance, as approximately 50% of apparent resistant hypertension cases are actually white-coat effect or medication nonadherence. 1

• If ambulatory monitoring is unavailable, use home BP monitoring as an alternative 1
• Verify medication adherence through direct questioning, pill counts, or pharmacy records 1
• Ensure proper BP measurement technique using appropriate cuff size and correct patient positioning 1

Optimize the Three-Drug Foundation

Your baseline regimen must include a renin-angiotensin system blocker (ACE inhibitor or ARB), a long-acting dihydropyridine calcium channel blocker, and a diuretic—all at maximal or maximally tolerated doses. 1

Critical Diuretic Selection:

• Switch from standard thiazides to thiazide-like diuretics (chlorthalidone or indapamide), as these are significantly more effective in resistant hypertension 1, 2
• If eGFR <30 mL/min/1.73m² or clinical volume overload is present, switch to loop diuretics, as unrecognized volume overload is a common cause of treatment failure 1, 3

Implement Aggressive Lifestyle Modifications

Restrict sodium intake to <2400 mg/day (ideally <1500 mg/day), as high sodium is a major contributor to treatment resistance. 1, 3

• Encourage weight loss if BMI >25 kg/m², which produces significant BP reductions 1, 3
• Limit alcohol to ≤2 drinks/day for men and ≤1 drink/day for women 1
• Implement structured regular physical activity 1

Screen for Secondary Causes

Screen for primary aldosteronism even with normal potassium levels, particularly in patients <30 years old. 1, 3

• Evaluate for obstructive sleep apnea using Berlin Questionnaire or Epworth Sleepiness Score, confirming with polysomnography if suspected 1
• Assess renal function including baseline eGFR and screen for renal artery stenosis with kidney ultrasound, followed by renal artery imaging if clinically indicated 1, 3
• Check TSH to evaluate for thyroid dysfunction 1, 3

Add Spironolactone as Fourth-Line Agent

Add spironolactone 25 mg daily as the preferred fourth-line agent, as it has demonstrated superior efficacy in resistant hypertension compared to all alternatives. 1, 3, 4

Eligibility and Monitoring:

• Ensure serum potassium <4.5 mmol/L and eGFR >45 mL/min/1.73m² before initiating 2
• Monitor serum potassium and renal function 1-2 weeks after initiation, especially when combining with RAS blockade 1, 2
• Use caution if eGFR <30 mL/min/1.73m² due to hyperkalemia risk 1

Alternative Fourth-Line Agents (if spironolactone contraindicated or not tolerated):

• Eplerenone, amiloride, doxazosin, clonidine, or beta-blocker 3, 4

Target Blood Pressure Goals

Target BP <130/80 mmHg and achieve this within 3 months of initiating or adjusting therapy. 3

• Reassess BP response within 2-4 weeks of any medication adjustment 1, 3
• Continue home BP monitoring to guide medication titration and improve adherence 1

Common Pitfalls to Avoid

Never combine ACE inhibitors with ARBs, as this does not reduce cardiovascular events and increases adverse effects. 2

• Do not use standard thiazides when thiazide-like diuretics (chlorthalidone/indapamide) are available, as the latter are superior for resistant hypertension 2
• Never add spironolactone without checking potassium and renal function due to hyperkalemia risk 2
• Do not assume resistance without confirming with ambulatory or home BP monitoring 1

When to Refer

Refer to a specialist center with expertise in resistant hypertension if BP remains uncontrolled after optimizing the four-drug regimen. 3

• Consider referral for evaluation of novel therapies including renal denervation in true resistant cases where all pharmacological options have been exhausted 5, 6