Management of Resistant Hypertension
For patients with resistant hypertension, a comprehensive approach including confirmation of true resistance, optimization of lifestyle modifications, and a strategic medication regimen with spironolactone as the preferred fourth-line agent is recommended.
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, including a long-acting calcium channel blocker, a blocker of the renin-angiotensin system, and a diuretic at maximal or maximally tolerated doses 1
- Confirm true resistance by performing 24-hour ambulatory blood pressure monitoring to exclude white-coat effect 1, 2
- Assess medication adherence, which accounts for approximately 50% of apparent treatment resistance 1
- Evaluate for secondary causes of hypertension, including obstructive sleep apnea, primary aldosteronism, and renovascular disease 2, 3
Initial Management Approach
Optimize Lifestyle Modifications
- Implement dietary salt restriction to less than 2400 mg/day 4, 1
- Encourage weight loss, which can lead to significant blood pressure reductions (10-kg weight loss associated with 6.0-mm Hg systolic and 4.6-mm Hg diastolic reduction) 4, 5
- Recommend regular physical exercise 5, 6
- Moderate alcohol intake 4
- Ensure adequate sleep (at least 6 hours of uninterrupted sleep) 2
- Consider supervised multidisciplinary lifestyle intervention programs, which have shown significant reductions in both systolic and diastolic blood pressure 6
Optimize Medication Regimen
- Simplify regimen to improve adherence, using long-acting combination products when possible 4
- Ensure optimal dosing of the three baseline medications 1, 7:
- Long-acting calcium channel blocker
- Renin-angiotensin system blocker (ACE inhibitor or ARB)
- Diuretic (preferably chlorthalidone or another thiazide-like diuretic) 8
Fourth-Line Treatment Strategy
- Add spironolactone 25mg daily as the preferred fourth-line agent 1, 2, 7
- Monitor serum potassium and renal function 1-2 weeks after initiating spironolactone, particularly with existing RAS blockade 2
- If spironolactone is not tolerated, consider these alternatives 1, 7, 3:
- Eplerenone (alternative mineralocorticoid receptor antagonist)
- Amiloride
- Alpha-blocker (e.g., doxazosin)
- Beta-blocker
- Clonidine
Monitoring and Follow-up
- Assess blood pressure response within 2-4 weeks of medication adjustment 2
- Monitor for target organ damage, including cardiac, renal, ocular, and peripheral vascular damage 2
- Consider home blood pressure monitoring to improve adherence and treatment effectiveness 4
Special Considerations
- For Black patients, initial antihypertensive treatment should include a diuretic or a calcium channel blocker 1
- For patients with heart failure, include ACE inhibitor/ARB, beta-blocker, diuretic, and/or mineralocorticoid receptor antagonist 1
- For patients with chronic kidney disease, target SBP 120-129 mmHg if eGFR >30 mL/min/1.73m² 1
Common Pitfalls and Caveats
- Pseudo-resistance is common and must be excluded before diagnosing true resistant hypertension 1, 2
- High sodium intake significantly contributes to treatment resistance 1
- Medications like NSAIDs, certain antidepressants, and stimulants can interfere with BP control 1
- Volume overload due to insufficient diuretic therapy is a common cause of treatment failure 4
- Consider multidisciplinary treatment approach including nurse case managers, pharmacists, and nutritionists to improve outcomes 4