What is the best next step for managing hypertension in a patient with a blood pressure of 170 mmHg on losartan (angiotensin II receptor blocker) 100mg and hydrochlorothiazide (HCTZ) (thiazide diuretic) 25mg, who cannot take amlodipine (Norvasc) (calcium channel blocker) due to leg swelling?

Management of Resistant Hypertension with BP 170 mmHg on Maximum Losartan and HCTZ

For a patient with blood pressure of 170 mmHg who is already on maximum doses of losartan 100mg and hydrochlorothiazide 25mg, and cannot tolerate amlodipine due to leg swelling, the best next step is to add spironolactone 25mg daily as a third-line agent.

Current Medication Assessment

• Patient is currently on:
  • Losartan 100mg daily (maximum FDA-approved dose) 1
  • HCTZ 25mg daily (maximum recommended dose in combination therapy) 1
• Previous trial of amlodipine (calcium channel blocker) resulted in leg swelling
• Current BP of 170 mmHg indicates resistant hypertension, defined as BP remaining >160/100 mmHg despite optimal doses of 2 drugs 2

Recommended Treatment Algorithm

Step 1: Add Spironolactone

• Add spironolactone 25mg daily
• Spironolactone is the recommended add-on therapy for resistant hypertension 2
• Particularly effective when added to an ARB (losartan) and thiazide diuretic (HCTZ) combination

Step 2: Monitor Response and Laboratory Values

• Check blood pressure within 2-4 weeks of medication adjustment
• Monitor serum potassium and renal function within 2-4 weeks after adding spironolactone 2
• Target blood pressure should be <160/100 mmHg acutely and <130/80 mmHg long-term

Step 3: Dose Adjustment

• If blood pressure remains elevated and no adverse effects:
  • Consider increasing spironolactone to 50mg daily
• If hyperkalemia or other adverse effects occur:
  • Consider alternative third-line agent

Alternative Options if Spironolactone is Contraindicated or Not Tolerated

Option 1: Beta-Blocker

• Consider metoprolol succinate or bisoprolol
• Note: Beta-blockers are not first-line unless patient has ischemic heart disease or heart failure 2
• Monitor for fatigue and sexual dysfunction

Option 2: Alpha-Blocker

• Consider doxazosin as an alternative third-line agent
• Monitor for orthostatic hypotension, especially in elderly patients 2

Option 3: Direct Vasodilator

• Consider hydralazine or minoxidil for severe resistant hypertension
• Requires close monitoring due to potential for significant side effects

Rationale for Recommendation

1. Triple drug regimen of ARB, thiazide diuretic, and a third agent is effective for resistant hypertension 2
2. Spironolactone has shown superior efficacy as a third-line agent in resistant hypertension
3. The patient has already failed calcium channel blocker therapy due to edema
4. Maximum doses of losartan (100mg) and HCTZ (25mg) are already being used 1

Important Monitoring Considerations

• Regular monitoring of serum potassium and renal function is essential with spironolactone
• Follow-up BP checks within 2-4 weeks of medication adjustment
• Monitor for gynecomastia with spironolactone (more common in men)
• Annual monitoring of microalbumin/creatinine ratio to detect early kidney damage 2

Lifestyle Modifications

• Reinforce sodium restriction (<2,300 mg/day)
• Recommend DASH or Mediterranean diet
• Encourage regular physical activity (150 minutes/week of moderate-intensity exercise)
• Address weight management if applicable
• Limit alcohol consumption
• Encourage smoking cessation if applicable 2

If blood pressure remains greater than 160/100 mmHg despite the addition of spironolactone at optimal doses, consider referral to a specialist with expertise in hypertension management 2.