What are the next best steps for managing hypertension in a patient on diltiazem and Diovan (valsartan) who cannot tolerate hydrochlorothiazide (HCTZ), atenolol, or olmesartan?

Management of Hypertension in a Patient on Diltiazem and Diovan with Multiple Medication Intolerances

For a patient on diltiazem 240mg and Diovan 320-25mg who cannot tolerate HCTZ, atenolol, or olmesartan, the most appropriate next step is to discontinue diltiazem (which is contraindicated in heart failure) and add a mineralocorticoid receptor antagonist such as spironolactone or eplerenone.

Current Medication Analysis

The patient is currently on:

• Diltiazem 240mg (non-dihydropyridine calcium channel blocker)
• Diovan 320-25mg (valsartan/HCTZ combination)

However, there are several concerns with the current regimen:

1. Diltiazem is contraindicated in patients with heart failure due to its negative inotropic properties 1. Guidelines specifically state: "Drugs to avoid in patients with HF and hypertension are nondihydropyridine CCBs (such as verapamil and diltiazem)" 1.

2. The patient is reportedly intolerant to HCTZ, yet is on Diovan 320-25mg which contains HCTZ (25mg).

Recommended Medication Changes

Step 1: Discontinue Diltiazem

• Diltiazem should be discontinued due to its contraindication in heart failure and replaced with a more appropriate agent 1.

Step 2: Consider Alternative Agents

Based on guidelines, the following options should be considered:

1. Add a Mineralocorticoid Receptor Antagonist (MRA):

   • Spironolactone 25mg daily is recommended as the first choice for resistant hypertension 1.
   • If spironolactone is not tolerated, eplerenone can be substituted 1.

2. Consider a Dihydropyridine CCB:

   • Unlike non-dihydropyridine CCBs (diltiazem, verapamil), dihydropyridine CCBs such as amlodipine are safe in heart failure 1.
   • Amlodipine can be added at 5-10mg daily 1.

3. Alpha-Blocker Option:

   • Doxazosin can be considered if other agents are inadequate for BP control 1.

Treatment Algorithm

1. First-line modification: Replace diltiazem with spironolactone 25mg daily

   • Monitor serum potassium closely due to potential hyperkalemia risk when combined with valsartan 2

2. If BP remains uncontrolled or spironolactone is not tolerated:

   • Try eplerenone 50mg daily as an alternative to spironolactone 1
   • OR add amlodipine 5-10mg daily 1

3. For truly resistant hypertension:

   • Consider adding doxazosin 1-8mg daily 1
   • OR hydralazine 25-100mg in divided doses 1

Important Monitoring Considerations

• Potassium monitoring: Essential when using spironolactone or eplerenone with valsartan due to increased risk of hyperkalemia 2
• Renal function: Monitor regularly, especially when modifying RAS blockers
• Blood pressure targets: Aim for BP <130/80 mmHg 1

Cautions and Contraindications

• Avoid combining ACE inhibitors with ARBs (like valsartan) as dual RAS blockade increases adverse effects without additional benefit 1, 2
• The patient's intolerance to HCTZ needs clarification since they are currently on a combination product containing HCTZ
• If the patient truly cannot tolerate any dose of HCTZ, consider switching to valsartan alone (without HCTZ component)

Rationale for Recommendations

The 2024 ESC guidelines specifically recommend spironolactone as the preferred add-on therapy for resistant hypertension 1. This approach is supported by the AHA guidelines which emphasize that non-dihydropyridine CCBs like diltiazem should be avoided in heart failure patients 1. The recommendation to discontinue diltiazem is further strengthened by its specific mention as a drug to avoid in the AHA Scientific Statement 1.