What is the next best treatment for a 75-year-old male with uncontrolled hypertension (blood pressure 158/108 mmHg) on losartan (angiotensin II receptor antagonist), tamsulosin (alpha-1 adrenergic blocker), furosemide (loop diuretic), and metoprolol (beta-blocker)?

Optimizing Uncontrolled Hypertension in a 75-Year-Old Male

Add spironolactone 25 mg once daily as the fourth-line agent for this patient with resistant hypertension, while closely monitoring serum potassium and renal function. 1

Current Regimen Assessment

This patient has resistant hypertension, defined as blood pressure remaining above target (158/108 mmHg) despite treatment with three antihypertensive agents including a diuretic. 2 His current regimen includes:

• Losartan (angiotensin receptor blocker)
• Furosemide (loop diuretic)
• Metoprolol (beta-blocker)
• Tamsulosin (alpha-1 blocker for BPH, minimal antihypertensive effect)

Critical Medication Optimization Before Adding Fourth Agent

Replace Furosemide with Chlorthalidone

Before adding a fourth agent, replace furosemide with chlorthalidone 12.5-25 mg daily, as thiazide-like diuretics are superior to loop diuretics for resistant hypertension unless the patient has significant chronic kidney disease (creatinine clearance <30 mL/min). 3, 1

• Loop diuretics like furosemide are short-acting and typically require twice-daily dosing, making them less effective for sustained blood pressure control 3
• Chlorthalidone provides superior 24-hour blood pressure reduction compared to hydrochlorothiazide, with the largest difference occurring overnight 3
• Chlorthalidone has demonstrated superior outcomes in resistant hypertension trials 1
• Important caveat: In elderly patients, start with chlorthalidone 12.5 mg to minimize risk of hypokalemia, which occurs 3-fold more frequently at doses above 12.5 mg 4
• Monitor serum potassium and creatinine 2-4 weeks after initiating the diuretic 1

Consider Adding Calcium Channel Blocker

If not already maximized, consider adding amlodipine 5-10 mg daily to complete the evidence-based triple therapy (ARB + calcium channel blocker + thiazide diuretic) before proceeding to fourth-line agents. 1, 4

• Dihydropyridine calcium channel blockers are well-tolerated in elderly patients and do not cause bradycardia 4
• Start with amlodipine 2.5-5 mg in elderly patients and titrate gradually to minimize vasodilatory side effects 4

Fourth-Line Agent: Mineralocorticoid Receptor Antagonist

Once the regimen includes optimal doses of an ARB, calcium channel blocker, and thiazide-like diuretic, add spironolactone 25-50 mg once daily as the preferred fourth-line agent. 1, 2

Evidence Supporting Spironolactone

• The PATHWAY-2 trial and multiple meta-analyses demonstrate spironolactone has the strongest evidence base for resistant hypertension 2, 5
• Spironolactone is efficacious in patients with heart failure, chronic kidney disease, and primary aldosteronism 5
• Patients with resistant hypertension often have occult volume expansion and aldosterone excess contributing to treatment resistance 3

Monitoring Requirements

• Check serum potassium and creatinine at baseline, then 2-4 weeks after initiation 1
• Monitor for hyperkalemia, particularly in elderly patients and those with chronic kidney disease 1
• If the patient has stage G3a CKD (as in the case example), SGLT2 inhibitors can reduce the risk of serious hyperkalemia when used with RAAS inhibitors and mineralocorticoid receptor antagonists 3

Alternative Fourth-Line Options

If spironolactone is contraindicated or not tolerated, consider these alternatives in order of preference: 2, 5

1. Amiloride (potassium-sparing diuretic without hormonal effects)
2. Doxazosin (alpha-blocker with antihypertensive benefit beyond tamsulosin)
3. Eplerenone (selective mineralocorticoid receptor antagonist with lower risk of gynecomastia)

Blood Pressure Target for This Patient

Target blood pressure <130/80 mmHg for this 75-year-old patient if well-tolerated, with a minimum acceptable target of <140/90 mmHg. 4, 6

• For relatively healthy older adults aged 65-80 years, target <140/90 mmHg is appropriate 4
• If well-tolerated and the patient has high cardiovascular risk, consider targeting <130/80 mmHg 4, 6
• Monitor for orthostatic hypotension by checking blood pressure in both sitting and standing positions at each visit 4

Critical Pitfalls to Avoid

• Never use loop diuretics as first-line therapy for resistant hypertension unless creatinine clearance <30 mL/min 3
• Avoid chlorthalidone doses >25 mg in elderly patients due to significantly increased risk of hypokalemia and minimal additional blood pressure benefit 4
• Do not add a fourth medication before optimizing the doses of existing agents and ensuring appropriate drug classes are being used 4
• Monitor for hyperkalemia when combining spironolactone with losartan, especially in elderly patients 1

Follow-Up Timeline

• Reassess blood pressure within 2-4 weeks after each medication adjustment 1, 4
• Achieve target blood pressure within 3 months of treatment modification 1, 4
• Reinforce sodium restriction to <2 g/day and promote lifestyle modifications (weight loss, regular aerobic exercise, DASH diet) for an additive 10-20 mmHg blood pressure reduction 1