From the Guidelines
Carvedilol is a highly effective beta-blocker that reduces morbidity and mortality in patients with heart failure, and its use is recommended for all patients with current or prior symptoms of HFrEF, unless contraindicated, due to its ability to block beta-1, beta-2, and alpha-1 adrenergic receptors. The standard dosing for carvedilol starts at 3.125 mg twice daily for heart failure, gradually increasing to 25-50 mg twice daily as tolerated [ 1 ]. For hypertension, the initial dose is typically 6.25 mg twice daily, with a maximum of 25 mg twice daily. Carvedilol's effectiveness stems from its unique pharmacological profile, which provides advantages over selective beta-blockers, particularly in heart failure where the additional vasodilation reduces afterload [ 1 ]. Some key points to consider when using carvedilol include:
- Its beta-1 blocking activity reduces heart rate and contractility, decreasing cardiac output and oxygen demand
- Its beta-2 blocking activity affects bronchial and vascular smooth muscle
- Its alpha-1 blockade causes vasodilation, further reducing blood pressure
- It possesses antioxidant properties that may protect against free radical damage
- Common side effects include dizziness, fatigue, hypotension, and bradycardia
- It should be used cautiously in patients with asthma, COPD, diabetes, or peripheral vascular disease due to its non-selective beta-blocking properties [ 1 ]. The benefits of carvedilol were seen in patients with or without CAD and in patients with or without diabetes mellitus, as well as in women and blacks [ 1 ]. Overall, carvedilol is a valuable treatment option for patients with heart failure and hypertension, and its use should be considered in accordance with current guidelines and patient-specific factors [ 1 ].
From the FDA Drug Label
Carvedilol Tablet is a racemic mixture in which nonselective β-adrenoreceptor blocking activity is present in the S(-) enantiomer and α1-adrenergic blocking activity is present in both R(+) and S(-) enantiomers at equal potency. β-adrenoreceptor blocking activity has been demonstrated in animal and human studies showing that Carvedilol Tablet (1) reduces cardiac output in normal subjects; (2) reduces exercise- and/or isoproterenol-induced tachycardia; and (3) reduces reflex orthostatic tachycardia. Demethylation and hydroxylation at the phenol ring produce 3 active metabolites with β-receptor blocking activity Based on preclinical studies, the 4'-hydroxyphenyl metabolite is approximately 13 times more potent than Carvedilol Tablet for β-blockade.
Carvedilol has nonselective β-adrenoreceptor blocking activity present in the S(-) enantiomer. The β-adrenoreceptor blocking activity of Carvedilol reduces:
- Cardiac output in normal subjects
- Exercise- and/or isoproterenol-induced tachycardia
- Reflex orthostatic tachycardia The active metabolites of Carvedilol also exhibit β-receptor blocking activity, with the 4'-hydroxyphenyl metabolite being approximately 13 times more potent than Carvedilol for β-blockade 2.
From the Research
Carvedilol and Beta Receptors
- Carvedilol competitively blocks beta 1, beta 2, and alpha 1 receptors 3
- The drug lacks sympathomimetic activity and has vasodilating properties that are exerted primarily through alpha 1-blockade 3
- Carvedilol distinguishes from other beta-blockers as being a non-selective beta(1)- and beta(2)-receptor blocker with alpha(1)-receptor blockade effect and anti-oxidant properties 4
Mechanism of Action
- Carvedilol reduces peripheral vascular resistance by blocking arterial alpha 1-adrenoceptors, thereby producing vasodilation, while preventing reflex tachycardia by blocking cardiac beta 1- and beta 2-adrenoceptors 5
- The drug has antioxidant and antiproliferative effects, which may contribute to its beneficial effects in chronic heart failure (CHF) 6
Clinical Effects
- Carvedilol improves left ventricular ejection fraction (LVEF) in patients with CHF 7, 6
- The drug reverses or attenuates left ventricular remodelling in patients with CHF and in those with left ventricular dysfunction after acute myocardial infarction (MI) 7, 6
- Carvedilol reduces mortality and morbidity in patients with mild to severe CHF 3, 4, 7, 6