What is carvedilol?

What is Carvedilol?

Carvedilol is a third-generation beta-blocker with combined alpha-1, beta-1, and beta-2 adrenergic blocking properties, plus antioxidant activity, approved for treating hypertension and heart failure. 1

Mechanism of Action

Carvedilol works through multiple complementary mechanisms that distinguish it from traditional beta-blockers:

• Blocks alpha-1 adrenergic receptors, causing peripheral vasodilation and reducing afterload without reflex tachycardia 2, 1
• Blocks beta-1 and beta-2 adrenergic receptors in the heart, reducing heart rate, contractility, and myocardial oxygen demand 2
• Possesses potent antioxidant properties through its carbazol moiety, inhibiting lipid peroxidation and scavenging oxygen free radicals—activity significantly greater than vitamin E 3, 4
• Inhibits vascular smooth muscle cell proliferation and migration, potentially slowing atherogenesis 5

Clinical Indications

Heart Failure with Reduced Ejection Fraction

Carvedilol is one of only four beta-blockers proven to reduce mortality in heart failure (along with metoprolol succinate, bisoprolol, and nebivolol):

• Reduces all-cause mortality by 65% in patients with mild to moderate heart failure 2, 3
• Reduces mortality risk by 38% and death/hospitalization by 31% in severe heart failure (NYHA class III-IV) in the COPERNICUS trial 6
• Provides 17% greater mortality reduction compared to metoprolol tartrate in head-to-head comparison 6
• Effective across all heart failure severities, including patients with ejection fraction <35-40% 2

Hypertension

• Reduces blood pressure through combined vasodilation and beta-blockade without compromising cardiac output or renal function 7, 8
• Particularly beneficial in hypertensive patients with concurrent heart failure or left ventricular dysfunction 6
• Has neutral effects on lipid and glucose metabolism, making it advantageous in diabetic patients 6, 8

Post-Myocardial Infarction

• Approved for patients with left ventricular dysfunction following myocardial infarction 1
• The CAPRICORN study demonstrated mortality benefit when added to ACE inhibitors in post-MI patients with ejection fraction <40% 2

Dosing and Administration

Must be taken with food to minimize side effects 1:

• Starting dose: 3.125 mg twice daily for heart failure; 6.25 mg twice daily for hypertension 1
• Target dose: 25 mg twice daily (higher doses show greater left ventricular functional benefits in the MOCHA trial) 6
• Titration: Increase gradually every 2 weeks as tolerated, monitoring for hypotension, bradycardia, and fluid retention 6

Important Safety Considerations

Contraindications

Do not use carvedilol in patients with 1:

• Severe decompensated heart failure requiring inotropic support
• Asthma or severe bronchospastic disease
• Bradycardia (heart rate <55 bpm) or high-degree heart block
• Severe liver dysfunction
• Cardiogenic shock

Common Adverse Effects

• Dizziness and orthostatic hypotension due to alpha-1 blockade—patients should sit or lie down if symptomatic 6, 1
• Fatigue and bradycardia from beta-blockade 1
• Fluid retention in early treatment—may require diuretic adjustment 6
• Decreased lacrimation affecting contact lens wearers 1

Critical Warnings

• Never discontinue abruptly—risk of rebound myocardial ischemia, infarction, and arrhythmias; taper gradually over 1-2 weeks 6, 1
• Monitor diabetic patients closely—may mask hypoglycemia symptoms, though metabolic effects are more favorable than other beta-blockers 6, 1
• Inform surgeons before cataract surgery—carvedilol can cause intraoperative floppy iris syndrome 1

Unique Advantages Over Other Beta-Blockers

Carvedilol's multiple mechanisms provide benefits beyond blood pressure and heart rate control:

• Cardioprotective effects through antioxidant activity, reducing oxidative stress in failing myocardium 3, 4
• Prevents LDL oxidation, potentially slowing atherosclerosis progression 4, 5
• Preserves endothelial function and inhibits vascular remodeling 5
• Maintains cardiac output despite negative inotropic effects, due to afterload reduction from vasodilation 4
• More favorable metabolic profile with less impact on glycemic control compared to traditional beta-blockers 6