What is the role of doxazosin in treating coronary artery disease (CAD)?

Doxazosin is Not Recommended for Treating Coronary Artery Disease

Doxazosin is not recommended for the treatment of coronary artery disease (CAD) and may increase the risk of congestive heart failure in patients with CAD. 1

Evidence Against Doxazosin Use in CAD

• The ALLHAT (Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial) demonstrated that doxazosin was associated with a significantly increased risk for congestive heart failure compared to chlorthalidone in patients with hypertension 1
• Doxazosin was also associated with significant weight gain, likely due to extracellular fluid volume expansion 1
• Alpha-blockers as a class are associated with asthenia, which might contribute to weight gain by altering energy balance 1
• Alpha-blockers are not recommended as first-line antihypertensive treatment for patients with CAD 1

Preferred Antihypertensive Medications for CAD Patients

First-Line Agents

• Beta-blockers are recommended as first-line therapy for hypertension in patients with CAD, particularly those with a history of prior myocardial infarction 1, 2
• ACE inhibitors or ARBs are recommended in patients with CAD who also have:
  • Left ventricular dysfunction
  • Diabetes mellitus
  • Chronic kidney disease 1, 2
• Thiazide or thiazide-like diuretics are recommended as part of the antihypertensive regimen 1

Second-Line Agents

• If beta-blockers are contraindicated or produce intolerable side effects, a non-dihydropyridine calcium channel blocker (such as diltiazem or verapamil) may be substituted, but not if there is left ventricular dysfunction 1, 2
• Long-acting dihydropyridine calcium channel blockers can be added if angina or hypertension remains uncontrolled on the basic regimen 1

Blood Pressure Targets in CAD

• For patients with stable angina, the blood pressure target is <140/90 mmHg 1
• A lower target (<130/80 mmHg) may be considered in some individuals with CAD, especially those with previous stroke, transient ischemic attack, or CAD risk equivalents 1, 2

Doxazosin's Approved Indications

• FDA-approved indications for doxazosin include:
  • Treatment of benign prostatic hyperplasia (BPH) 3
  • Treatment of hypertension 3
• There is no FDA-approved indication for doxazosin in the treatment of CAD 3

Mechanism of Action

• Doxazosin works through selective blockade of alpha-1 (postjunctional) adrenergic receptors 3
• The antihypertensive effect results from a decrease in systemic vascular resistance 3
• While this mechanism can lower blood pressure, it does not provide the specific cardioprotective benefits needed for CAD patients 3

Clinical Considerations

• When treating hypertension in patients with CAD, medications should be selected based on their ability to both lower blood pressure and provide cardioprotective effects 1
• Most patients with CAD and hypertension will require two or more antihypertensive medications to achieve blood pressure goals 2
• The combination of medications should be carefully selected to avoid adverse effects and provide complementary mechanisms of action 1

Conclusion

For patients with CAD requiring antihypertensive therapy, beta-blockers, ACE inhibitors/ARBs, and thiazide diuretics should be prioritized over alpha-blockers like doxazosin. The evidence clearly shows that doxazosin is associated with increased risk of heart failure in this population and lacks the cardioprotective benefits of other antihypertensive classes.