For a patient with uncontrolled hypertension on losartan (angiotensin II receptor antagonist) 100mg - hydrochlorothiazide (HCTZ) (thiazide diuretic) 25mg and amlodipine (calcium channel blocker) 5mg, should I increase the dose of amlodipine and add metoprolol (beta-blocker)?

Management of Uncontrolled Hypertension on Triple Therapy

For a patient with uncontrolled hypertension on losartan 100mg-HCTZ 25mg and amlodipine 5mg, you should increase amlodipine to 10mg and add spironolactone rather than metoprolol as the fourth agent. 1

Current Medication Assessment

• The patient is currently on a three-drug regimen that includes:
  • An ARB (losartan 100mg) - already at maximum recommended dose 2
  • A thiazide diuretic (HCTZ 25mg) - already at optimal dose 1
  • A calcium channel blocker (amlodipine 5mg) - not yet at maximum dose 3

Step 1: Optimize Current Medications

• Increase amlodipine from 5mg to 10mg daily 3
  • Amlodipine can be safely titrated to 10mg daily for better BP control 3
  • The FDA label indicates a titration period of 7-14 days between dose adjustments 3
  • Maximizing the CCB dose before adding a fourth agent is recommended by hypertension guidelines 1

Step 2: Add Fourth Agent (Resistant Hypertension)

• Add spironolactone 25mg daily as the preferred fourth agent 1
  • Spironolactone is the recommended first choice for resistant hypertension according to the 2020 ISH guidelines 1
  • Spironolactone has shown superior efficacy compared to other fourth-line agents in resistant hypertension 1
  • Monitor for hyperkalemia, especially in combination with an ARB 1

Why Not Metoprolol?

• Beta-blockers (like metoprolol) are not preferred as fourth-line agents for resistant hypertension 1
  • They are listed after spironolactone, amiloride, doxazosin, and eplerenone in treatment algorithms 1
  • Beta-blockers may be associated with adverse metabolic effects and reduced cardiovascular protection compared to other agents 1
  • They should be considered only if spironolactone is contraindicated or not tolerated 1

Monitoring and Follow-up

• Reassess blood pressure control within 2-4 weeks after medication changes 1
• Monitor serum potassium and renal function within 1-2 weeks after adding spironolactone 1
• Target BP should be <130/80 mmHg for most patients 1
• If BP remains uncontrolled despite optimized four-drug therapy, consider referral to a hypertension specialist 1

Important Considerations

• Check medication adherence before adding new agents 1
• Evaluate for secondary causes of hypertension if BP remains difficult to control 1
• Consider once-daily dosing and single-pill combinations when possible to improve adherence 1
• Lifestyle modifications should continue to be emphasized alongside pharmacotherapy 1