What is the best next step for a patient with uncontrolled hypertension on hydrochlorothiazide (HCTZ) 25mg and losartan 100mg, who experienced lower leg swelling with amlodipine and has a pulse rate of 58 beats per minute (bradycardia)?

Management of Uncontrolled Hypertension with Bradycardia and Intolerance to Amlodipine

For a patient with uncontrolled hypertension on HCTZ 25mg and losartan 100mg, who experienced lower leg edema with amlodipine and has bradycardia (pulse 58 bpm), the best next step is to add spironolactone 25mg daily.

Assessment of Current Therapy

The patient is currently on:

• Hydrochlorothiazide 25mg (maximum recommended dose)
• Losartan 100mg (maximum recommended dose as per FDA labeling) 1

Despite this combination, the patient remains hypertensive, indicating resistant hypertension. Resistant hypertension is defined as blood pressure ≥140/90 mmHg despite three antihypertensive agents, including a diuretic 2.

Medication Selection Algorithm

1. First-line agents (already maximized):

   • ACE inhibitor/ARB (losartan 100mg - at maximum dose)
   • Thiazide diuretic (HCTZ 25mg - at maximum dose)

2. Second-line options (considering patient's characteristics):

   • Calcium channel blocker (previously tried amlodipine - caused edema)
   • Beta-blocker (contraindicated due to existing bradycardia - pulse 58 bpm)

3. Third-line option (recommended next step):

   • Mineralocorticoid receptor antagonist (spironolactone)

Evidence Supporting Spironolactone Addition

The European Society of Cardiology guidelines recommend a mineralocorticoid receptor antagonist when hypertension persists despite treatment with a combination of ACE inhibitor/ARB, beta-blocker, and diuretic 3. Specifically, spironolactone has shown significant antihypertensive benefit when added to existing multidrug regimens 3.

Studies have demonstrated that spironolactone can lower blood pressure by an additional 25/12 mmHg when added to regimens including a diuretic and ACE inhibitor/ARB 3. This effect was consistent across both African American and white patients, making it an appropriate choice regardless of racial background.

Why Not Other Options?

1. Amlodipine: Patient has history of lower leg edema with amlodipine, a common side effect of calcium channel blockers 3.

2. Beta-blockers: Patient's pulse is 58 bpm, indicating bradycardia, which is a contraindication to beta-blocker therapy as it would further lower heart rate.

3. Increasing current medications: Both losartan and HCTZ are already at maximum recommended doses 1.

4. Other calcium channel blockers: While felodipine could be considered as it may cause less edema than amlodipine 4, the patient's bradycardia makes mineralocorticoid receptor antagonists a safer choice.

Monitoring Recommendations

When starting spironolactone:

1. Check baseline potassium and renal function
2. Recheck potassium and renal function within 1-2 weeks of initiation
3. Monitor for hyperkalemia, especially since the patient is already on an ARB (losartan)
4. Start at 25mg daily and titrate as needed based on blood pressure response

Important Precautions

• Hyperkalemia risk: Combination of spironolactone with ARBs increases risk of hyperkalemia. Monitor potassium levels closely 3.
• Renal function: Use with caution if creatinine >2.5 mg/dL 2.
• Dose adjustment: If 25mg is insufficient, dose can be increased, as studies show additional benefit at higher doses 3.

Alternative Options If Spironolactone Fails

If spironolactone is ineffective or not tolerated:

1. Hydralazine: Recommended by ESC guidelines when hypertension persists despite optimal therapy 3.
2. Felodipine: May cause less edema than amlodipine and is specifically mentioned in ESC guidelines as an option 3.
3. Amiloride: An alternative indirect aldosterone antagonist that has shown efficacy in resistant hypertension 3.

By following this approach, you can effectively manage this patient's resistant hypertension while avoiding medications that would worsen existing bradycardia or cause recurrence of lower extremity edema.