What is the next medication for a patient with uncontrolled hypertension despite taking losartan (angiotensin II receptor antagonist) 100 mg and metoprolol (beta blocker) tartrate 25 mg twice daily?

Next Medication for Uncontrolled Hypertension Despite Losartan and Metoprolol

For a patient with uncontrolled hypertension despite taking losartan 100 mg and metoprolol tartrate 25 mg twice daily, the next medication to add should be a thiazide/thiazide-like diuretic. 1

Treatment Algorithm Based on Current Medications

The patient is currently on:

• Losartan 100 mg (ARB at full dose)
• Metoprolol tartrate 25 mg twice daily (beta-blocker)

Step-by-Step Approach:

1. Add a thiazide/thiazide-like diuretic 1

   • This follows the recommended treatment algorithm for non-black patients who have already maximized ARB dosing
   • Examples include hydrochlorothiazide 12.5-25 mg or chlorthalidone 12.5-25 mg

2. If blood pressure remains uncontrolled after adding a thiazide diuretic:

   • Add spironolactone 25-50 mg daily 1
   • If spironolactone is not tolerated or contraindicated, consider:
     • Eplerenone 1
     • Amiloride 1
     • Doxazosin (alpha-blocker) 1

Evidence Supporting This Recommendation

The 2020 International Society of Hypertension (ISH) guidelines clearly outline a stepwise approach for treating resistant hypertension 1:

• For non-black patients, after maximizing ARB/ACEI dosage (which has been done with losartan 100 mg), the next step is to add a thiazide/thiazide-like diuretic 1
• The patient is already on a beta-blocker (metoprolol), which is typically added later in the treatment algorithm 1

Research evidence supports the efficacy of adding a thiazide diuretic to losartan for better blood pressure control:

• The combination of losartan with hydrochlorothiazide has been shown to be more effective than either drug alone 2, 3
• In patients with severe hypertension, approximately one-third responded to losartan/HCTZ alone, while others required additional agents 2

Important Clinical Considerations

• Check medication adherence before adding new medications 1
• Monitor electrolytes after starting a diuretic, especially potassium levels when combining with an ARB 3
• Target blood pressure should be <130/80 mmHg according to current guidelines 1
• Evaluate within 3 months to determine if blood pressure target is achieved 1

Special Considerations for Resistant Hypertension

If the patient's blood pressure remains elevated despite triple therapy (ARB + beta-blocker + thiazide diuretic), this would qualify as resistant hypertension, which requires:

• Reinforcement of lifestyle measures, especially sodium restriction 1
• Addition of spironolactone as the preferred fourth-line agent 1
• Consider referral to a hypertension specialist if blood pressure remains uncontrolled on four medications 1

Potential Pitfalls to Avoid

• Avoid inadequate dosing of the thiazide diuretic - start with appropriate doses (e.g., HCTZ 12.5-25 mg) 2, 3
• Don't overlook drug interactions between current medications and new additions 3
• Don't delay escalation of therapy if blood pressure remains uncontrolled 1
• Avoid assuming non-adherence without verification - medication adherence should be assessed but not assumed to be the only issue 1