The Role of Carvedilol in the Treatment of Dilated and Anthracyclines-Induced Cardiomyopathy

Abstract

Although chronic sympathetic activation provides inotropic and chronotropic support to the failing heart, such activation may also have deleterious effects, including the direct cardiotoxic effects of catecholamines, activation of the renin-angiotensin-aldosterone system and an increase in myocardial oxygen demand. These observations indicate that β-blockade might be beneficial in the treatment of heart failure resulting from dilated cardiomyopathy or ischaemic heart disease. Carvedilol is a non-selective β-blocker acting on β1-, β2-, and α1-adrenoceptors. It possesses potent anti-oxidant and anti-apoptotic properties, along with neuroprotective, vasculoprotective, cardioprotective effects, and it has reduced overall mortality in patients with heart failure in controlled clinical trials. Its role in treating cardiomyopathy requires focus. The fact that anthracyclines are cardiotoxic seriously narrows their therapeutic index in cancer therapy. The cardiotoxic risk increases with the cumulative dose and may lead to congestive heart failure and dilated cardiomyopathy in adults and in children. This review focuses on recent research regarding the beneficial effects of carvedilol in the treatment of dilated cardiomyopathy and to revisit the available evidence on the cardioprotection of carvedilol when associated with anthracycline and to explain the mechanisms underlying the benefits of their co-administration.

Diagnosis, Prognosis, Management, Treatment, Research and Advances in Canine Dilated Cardiomyopathy

“…Beta-blockers such as carvedilol have shown to have positive impacts for people with DCM [51][52][53]. Although carvedilol is a popular choice in humans with DCM and congestive heart failure [54,55], there is limited evidence to date that these are beneficial in canine breeds with DCM [56]. Where used, careful monitoring should be ensured and treatment is best tolerated in dogs during the early stages of DCM [42].…”

Antiapoptotic and Antioxidant Effects of Carvedilol and Vitamin E Protect Against Diabetic Nephropathy and Cardiomyopathy in Diabetic Wistar Albino Rats

“…Several carvedilol metabolites found in human plasma showed an even stronger antioxidant activity (50-80 times higher than carvedilol) [29]. Carvedilol has a direct inhibitory effect on exogenous nicotinamide adenine dinucleotide phosphate oxidase (NADPH), the enzyme that involved in ROS formation and downregulated matrix metalloproteinase (MMP)-2 expression in the myocardium [30].…”

“…found to increase endothelial NO synthesis and decrease TNFalpha induced VCAM-1 and ICAM-1 production [30]. The antiapoptotic effects of carvedilol has been suggested to be due to its ability to modulate the signaling pathway of the active genedirected process of cell suicide through suppression of stressactivated protein kinase (SAPK) (a proapoptotic kinase), suppression of caspase 3 (proapoptotic protease) as well as downregulation of the Fas expression (proapoptotic gene).…”

Comparison of protective effects of carvedilol and α-tocopherol on doxorubicin-induced cardiotoxocity

“…20,21 Carvedilol reduces morbidity and mortality in patients with chronic heart failure and inhibits cardiac remodeling It prevents the depletion of endogenous antioxidants, such as vitamin E and glutathione and prevents mitochondrial dysfunction caused by doxorubicin. 22,23 Carvedilol inhibits lipid peroxidation in myocardial cell membranes initiated by oxygen radicals. 24 At high dosages, carvedilol prevents ventricular tachycardia in heart failure associated with chemotherapy.…”