In a 71-year-old overweight woman taking hydrochlorothiazide, amlodipine, and olmesartan with a blood pressure of 150/80 mm Hg and normal potassium and renal function, should spironolactone be added?

Should Spironolactone Be Added?

Yes, add spironolactone 25 mg daily as the fourth-line agent after first optimizing your current regimen by replacing hydrochlorothiazide with chlorthalidone or indapamide, which are significantly more effective in resistant hypertension. 1

Step 1: Confirm True Treatment Resistance

Before adding any medication, you must rule out pseudoresistance:

• Perform 24-hour ambulatory blood pressure monitoring to exclude white-coat hypertension, which accounts for approximately 50% of apparent resistant cases 1
• If ambulatory monitoring is unavailable, use validated home blood pressure monitoring as an alternative 1
• Verify medication adherence and ensure proper BP measurement technique with correct cuff size 1

Step 2: Optimize Current Triple Therapy FIRST

Do not add spironolactone before optimizing your existing regimen: 1

• Replace hydrochlorothiazide with chlorthalidone 12.5–25 mg daily or indapamide 1.25–2.5 mg daily because thiazide-like diuretics are significantly more effective than standard thiazides in resistant hypertension 1
• Verify that olmesartan and amlodipine are at maximal or maximally tolerated doses 1
• This optimization alone may achieve BP control without adding a fourth agent 1

Step 3: Intensify Lifestyle Modifications

While optimizing medications:

• Restrict dietary sodium to <2,400 mg/day (ideally <1,500 mg/day), which can lower systolic BP by 10–20 mmHg 1
• Promote weight loss, as this patient is overweight and weight reduction significantly improves BP control 1
• Limit alcohol to ≤1 drink/day for women 1

Step 4: Add Spironolactone as Fourth-Line Agent

If BP remains ≥150/80 mmHg after optimizing the triple regimen and lifestyle measures:

• Initiate spironolactone 25 mg once daily as the preferred fourth-line agent based on superior efficacy demonstrated in the PATHWAY-2 trial 1
• Spironolactone provides significant additional BP reduction when added to multidrug regimens in resistant hypertension 2
• The combination of thiazide and potassium-sparing diuretics (including spironolactone) has been widely used to prevent potassium loss and may reduce sudden death incidence 2

Critical Monitoring Requirements

Before starting spironolactone:

• Confirm baseline potassium is <4.5 mmol/L and eGFR is adequate 1
• Do not initiate if baseline potassium ≥4.5 mmol/L or eGFR <45 mL/min/1.73 m² 1

After starting spironolactone:

• Check serum potassium and creatinine within 1–2 weeks, then regularly thereafter 1, 3
• More frequent monitoring is essential because this patient is taking olmesartan (an ARB), which significantly increases hyperkalemia risk when combined with spironolactone 3
• Monitor for gynecomastia, which occurs in approximately 9% of patients at mean doses of 26 mg daily 3

Common Pitfalls to Avoid

• Never add spironolactone before switching to a thiazide-like diuretic (chlorthalidone or indapamide), as this is the most critical optimization step 1
• Never skip ambulatory or home BP monitoring, as white-coat hypertension is extremely common in apparent resistant cases 1
• Never initiate spironolactone without confirming acceptable baseline potassium and renal function, especially in elderly patients on ARB therapy 1, 3
• Be aware that spironolactone can cause hyperkalemia, hyponatremia, hypotension, and worsening renal function, particularly when combined with ARBs 3

Alternative Fourth-Line Options

If spironolactone is contraindicated or not tolerated:

• Doxazosin 1–8 mg daily (alpha-blocker), starting at low dose to prevent first-dose orthostatic hypotension 1
• Eplerenone (selective mineralocorticoid receptor antagonist) with lower gynecomastia risk 1
• Beta-blocker if resting heart rate >70 bpm 1

When to Refer

• Refer to a hypertension specialist if BP remains >130/80 mmHg after at least 6 months of optimized triple therapy, as specialists achieve control in approximately 52–53% of resistant cases 1