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

Initial Treatment Approach for Resistant Hypertension

The initial treatment approach for patients with resistant hypertension should include adding a mineralocorticoid receptor antagonist (MRA), specifically spironolactone, as the fourth-line agent to the existing three-drug regimen of a renin-angiotensin system blocker, calcium channel blocker, and diuretic. 1, 2, 3

Confirming True Resistant Hypertension

Before initiating treatment, confirm the diagnosis of resistant hypertension:

• 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, 4
• Perform 24-hour ambulatory BP monitoring to exclude white-coat effect and confirm adherence 1, 2
• Assess for secondary causes of hypertension, particularly primary aldosteronism, obstructive sleep apnea, renal artery stenosis, and other endocrine disorders 1

Optimizing the Current Regimen

Before adding a fourth agent, ensure the current three-drug regimen is optimized:

• Verify patients are on optimal doses of a three-drug regimen including a long-acting calcium channel blocker, a renin-angiotensin system blocker (ACE inhibitor or ARB), and an appropriately dosed diuretic based on kidney function 1, 4
• Consider substituting a thiazide-like diuretic (chlorthalidone or indapamide) for hydrochlorothiazide, as these have superior 24-hour blood pressure control 1, 5
• Simplify medication regimen using long-acting combination products or fixed-dose single-pill combinations when possible to improve adherence 6, 1

Adding a Fourth-Line Agent

After optimizing the current regimen:

• Add spironolactone as the most effective fourth-line agent, starting at 25 mg daily 1, 2, 7
• If spironolactone is not tolerated due to side effects, use eplerenone as an alternative 1, 2
• Monitor serum potassium and renal function 1-2 weeks after initiating spironolactone, particularly when combining with an ACE inhibitor or ARB 2, 7

Lifestyle Modifications

Implement concurrent lifestyle modifications:

• Restrict dietary salt to less than 2400 mg/day, which can reduce systolic and diastolic blood pressure by 5-10 mmHg and 2-6 mmHg respectively 1, 4
• Encourage weight loss for overweight or obese patients, as a 10-kg weight loss is associated with average reductions of 6.0 mmHg systolic and 4.6 mmHg diastolic blood pressure 1, 8
• Recommend the DASH diet (rich in fruits, vegetables, low-fat dairy, and low in saturated fats) 6, 1
• Limit alcohol intake to no more than 2 drinks per day for men and 1 drink per day for women, or preferably avoid alcohol consumption entirely 6, 1
• Promote regular aerobic exercise for at least 30 minutes on most days of the week 1, 8

Common Pitfalls and Caveats

• Volume overload due to insufficient diuretic therapy is a common cause of treatment failure; ensure appropriate diuretic dosing 1, 4
• Poor medication adherence accounts for approximately 50% of apparent treatment resistance; consider pill counts, medication diaries, or directly observed therapy 1, 4
• Avoid medications that can interfere with blood pressure control, such as NSAIDs, certain antidepressants, and stimulants 1, 4
• Device-based therapies like renal denervation remain investigational and should be considered only after optimizing pharmacological therapy 6, 1
• Combining two RAS blockers (ACE inhibitor and an ARB) is not recommended 6, 9

Special Populations

• For patients with obstructive sleep apnea, CPAP therapy can significantly improve blood pressure control 1, 3
• African American patients may respond better to calcium channel blockers and diuretics than to renin-angiotensin system blockers 1, 4
• For patients with chronic kidney disease, monitor renal function and potassium levels closely when using spironolactone 4, 7