Which medication should be increased for continued hypertension: Cardura (doxazosin), amlodipine, clonidine, or hydralazine?

Medication Selection for Continued Hypertension

Amlodipine should be increased first for continued hypertension, as it has the strongest evidence for efficacy and safety among the options presented. 1

Prioritization of Antihypertensive Agents

When choosing which medication to increase for persistent hypertension, a stepwise approach based on guideline recommendations should be followed:

First-Line Agents (Preferred)

• Amlodipine (Calcium Channel Blocker)
  • Recommended as first-line therapy for hypertension 1
  • Proven safety in patients with heart failure 1
  • Demonstrated efficacy in reducing cardiovascular events 2
  • Can be safely titrated up to 10mg daily 3

Second-Line Agents

• Hydralazine
  • Recommended as a third-line agent after ACE inhibitors/ARBs, beta-blockers, and diuretics 1
  • Requires combination with a beta-blocker due to reflex tachycardia 1
  • Associated with sodium and water retention 1
  • Higher doses associated with drug-induced lupus-like syndrome 1

Third-Line or Last-Resort Agents

• Clonidine

  • Generally reserved as last-line due to significant CNS adverse effects 1
  • Risk of rebound hypertension with abrupt discontinuation 1
  • Potentially associated with increased mortality in heart failure patients 1

• Doxazosin (Cardura)

  • Associated with increased risk of heart failure 1
  • The doxazosin arm of the ALLHAT trial was discontinued due to 2.04-fold increased risk of heart failure compared to chlorthalidone 1
  • Associated with orthostatic hypotension, especially in older adults 1

Dosing Considerations

Amlodipine

• Starting dose: 2.5-5mg daily
• Can be titrated up to 10mg daily 1, 3
• Once-daily dosing improves adherence
• Demonstrated dose-dependent blood pressure reduction 3

Hydralazine

• Usual dose range: 100-200mg daily in 2-3 divided doses 1
• Must be used with a diuretic and beta-blocker to counteract sodium retention and reflex tachycardia 1

Clonidine

• Dose range: 0.1-0.8mg daily in 2 divided doses 1
• Must be tapered slowly when discontinuing to prevent hypertensive crisis 1

Doxazosin

• Dose range: 1-16mg once daily 1, 4
• Requires careful monitoring for orthostatic hypotension 1

Important Cautions and Contraindications

• Doxazosin: Avoid or use with extreme caution in patients with heart failure risk 1
• Clonidine: Avoid abrupt discontinuation; must taper to prevent rebound hypertension 1
• Hydralazine: Monitor for symptoms of lupus-like syndrome at higher doses; always use with beta-blocker 1

Blood Pressure Targets

• General target: <130/80 mmHg 1, 5
• For patients with heart failure, consider targeting SBP 110-130 mmHg 1
• Monitor BP within 48-72 hours after medication adjustment 5

Combination Therapy Considerations

If single-agent titration is insufficient, consider rational combinations:

• Amlodipine + ACE inhibitor or ARB is an effective combination 6
• Amlodipine + doxazosin has shown additive effects, but only if heart failure is not a concern 7
• Hydralazine is most effective when combined with a beta-blocker and diuretic 1

Conclusion

Based on the available evidence and guideline recommendations, amlodipine should be prioritized for dose increase due to its proven efficacy, favorable safety profile, and strong evidence for cardiovascular protection. The other agents (hydralazine, clonidine, and doxazosin) have more significant limitations and safety concerns that make them less desirable options for initial dose escalation.