What adjustments can be made to a patient's antihypertensive regimen consisting of Hydralazine HCL, Losartan Potassium, and Metoprolol Succinate ER, who remains hypertensive despite current therapy?

Optimizing Antihypertensive Therapy for Uncontrolled Hypertension

For a patient who remains hypertensive despite treatment with hydralazine 25 mg TID, losartan 75 mg daily, and metoprolol succinate ER 150 mg daily, the most effective adjustment would be to add a thiazide-like diuretic while simplifying the regimen to once-daily dosing when possible.

Current Regimen Analysis

The patient is currently on:

• Hydralazine 25 mg TID (vasodilator)
• Losartan 75 mg daily (ARB)
• Metoprolol succinate ER 150 mg daily (beta-blocker)

This regimen has several issues:

1. Missing a thiazide/thiazide-like diuretic, which is a critical component of combination therapy according to guidelines 1
2. Multiple daily dosing with hydralazine (TID), which may reduce compliance 2, 3
3. Suboptimal dosing strategy that doesn't follow the recommended stepped approach for resistant hypertension 1

Recommended Medication Adjustments

Step 1: Add a Thiazide-Like Diuretic

• Add chlorthalidone 12.5-25 mg once daily or indapamide 1.25-2.5 mg once daily
• Thiazide-like diuretics are recommended as part of the standard stepped approach for both black and non-black patients 1

Step 2: Optimize Current Medications

• Losartan: Continue at current dose (75 mg daily) or increase to maximum of 100 mg daily if needed 4
• Metoprolol succinate ER: Continue at current dose (150 mg daily)
• Hydralazine: Consider replacing with a once-daily calcium channel blocker (CCB) such as amlodipine 5-10 mg daily to improve compliance and efficacy 1
  • If hydralazine must be continued, maintain current dose

Step 3: If BP Remains Uncontrolled After 4 Weeks

• Add spironolactone 25-50 mg daily if serum potassium <4.5 mmol/L and eGFR >45 ml/min/1.73m² 1
• If spironolactone is contraindicated or not tolerated, consider adding one of the following:
  • Eplerenone 25-50 mg daily
  • Doxazosin 1-8 mg daily
  • Clonidine 0.1-0.3 mg twice daily

Rationale for Recommendations

1. Addition of a Thiazide-Like Diuretic:

   • The 2020 ISH guidelines clearly recommend adding a thiazide/thiazide-like diuretic as part of the stepped approach for both black and non-black patients 1
   • Thiazide-like diuretics enhance the efficacy of RAS blockers (losartan) and beta-blockers (metoprolol)

2. Simplification of Regimen:

   • Once-daily dosing significantly improves medication compliance (95% vs 74-84% for multiple daily dosing) 2
   • Poor compliance is a major cause of resistant hypertension 3

3. Consideration of Patient-Specific Factors:

   • Hydralazine TID dosing may contribute to poor compliance
   • Hydralazine can cause reflex tachycardia, which may counteract some of the beta-blocker effects 5
   • Replacing hydralazine with a once-daily CCB would simplify the regimen while maintaining vasodilatory effects

Monitoring Recommendations

• Reassess BP within 4 weeks after medication changes
• Target BP should be <130/80 mmHg 1
• Monitor electrolytes and renal function within 2 weeks of adding or adjusting diuretic therapy
• Assess for medication adherence at each visit
• If BP remains uncontrolled despite optimized 4-drug regimen, refer to a hypertension specialist 1

Common Pitfalls to Avoid

1. Failing to assess medication adherence:

   • Up to 50% of apparent resistant hypertension cases are due to poor adherence 1
   • Simplifying regimens improves adherence significantly 2, 3

2. Inadequate diuretic therapy:

   • Many patients with resistant hypertension have unrecognized volume expansion
   • Omitting a diuretic from the regimen is a common cause of treatment failure 1

3. Suboptimal dosing:

   • Losartan 100 mg provides greater BP reduction than lower doses 4
   • Using submaximal doses before adding new agents may lead to unnecessary polypharmacy

4. Drug interactions:

   • Be aware of potential interactions between multiple antihypertensives
   • Monitor for orthostatic hypotension when using multiple vasodilators

By following this stepped approach with careful monitoring, most patients with previously uncontrolled hypertension can achieve target blood pressure levels with improved medication adherence.