What is the optimal treatment approach for patients with resistant hypertension?

Optimal Treatment Approach for Resistant Hypertension

The optimal treatment approach for resistant hypertension includes a stepwise algorithm starting with confirmation of true resistance, optimization of a three-drug regimen, addition of spironolactone as fourth-line therapy, followed by sequential addition of other agents while addressing lifestyle factors and secondary causes. 1

Confirming True Resistant Hypertension

• Resistant hypertension is defined as blood pressure that remains above target (>130/80 mmHg) despite concurrent use of 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, 2
• Perform 24-hour ambulatory blood pressure monitoring to exclude white-coat effect and confirm adherence to therapy 1, 3
• Rule out pseudoresistance by assessing medication adherence, which accounts for approximately 50% of apparent treatment resistance 3, 4
• Screen for substances that may interfere with blood pressure control, such as NSAIDs, certain antidepressants, and stimulants 5, 6

Optimize Current Medication Regimen

• Ensure the three-drug regimen includes a renin-angiotensin system blocker (ACE inhibitor like lisinopril or ARB like losartan), a long-acting calcium channel blocker (like amlodipine), and an appropriately dosed diuretic 1, 7
• Substitute a thiazide-like diuretic (chlorthalidone or indapamide) for hydrochlorothiazide, as these maintain efficacy at lower estimated glomerular filtration rates (down to 30 mL/min/1.73m²) 1
• Consider using fixed-dose combination products to improve adherence 3, 5

Fourth-Line Therapy

• Add a mineralocorticoid receptor antagonist (MRA) like spironolactone (starting at 25 mg daily) as the preferred fourth-line agent 1, 3
• Monitor serum potassium and renal function within 1-2 weeks after starting spironolactone, particularly in patients with reduced kidney function 3, 5
• If spironolactone is not tolerated, consider eplerenone as an alternative MRA 1, 8

Additional Pharmacological Options

• If blood pressure remains uncontrolled, add a beta-blocker (unless heart rate <70 beats/min) or combined alpha-beta blocker 1, 6
• If beta-blockers are contraindicated, consider a central alpha-agonist (clonidine patch weekly or guanfacine at bedtime) 1
• For further escalation, add hydralazine (starting at 25 mg three times daily) and titrate upward to maximum dose 1
• As a last resort, consider minoxidil (starting at 2.5 mg two to three times daily) as a substitute for hydralazine 1

Lifestyle Modifications

• Implement dietary sodium restriction to less than 2400 mg/day 1, 3
• Encourage weight loss for overweight or obese patients, as a 10-kg weight loss can reduce systolic BP by 6.0 mmHg and diastolic BP by 4.6 mmHg 1
• Recommend regular physical activity (minimum 30 minutes on most days of the week) 1, 9
• Limit alcohol intake to no more than 2 drinks per day for men and 1 drink per day for women 1
• Promote a DASH diet (rich in fruits, vegetables, low-fat dairy products, and low in saturated fats) 1, 3

Address Secondary Causes

• Screen for common secondary causes of hypertension, particularly in patients with true resistant hypertension 1, 6:
  • Obstructive sleep apnea (consider CPAP therapy if diagnosed) 1
  • Primary aldosteronism 1, 8
  • Chronic kidney disease 5
  • Renovascular disease 8

Treatment Considerations for Special Populations

• For Black patients, initial treatment should include a diuretic or calcium channel blocker, either alone or in combination with a renin-angiotensin system blocker 3, 5, 10
• For patients with heart failure, include ACE inhibitors/ARBs, beta-blockers, diuretics, and/or mineralocorticoid receptor antagonists in the regimen 3, 5
• For patients with chronic kidney disease, use renin-angiotensin system blockers as part of the treatment strategy, especially with albuminuria 5

Common Pitfalls and Caveats

• Volume overload due to insufficient diuretic therapy is a common cause of treatment failure; ensure optimal diuretic use 3, 8
• Medication nonadherence affects 10-80% of hypertensive patients; simplify regimens when possible 5, 4
• The role of device-based therapies like renal denervation remains unclear and awaits further validation before routine clinical application 1, 6
• Consider referral to a hypertension specialist if blood pressure remains uncontrolled despite multiple medication adjustments 3, 5