Mechanisms Involved in the Cardiac Protection Efficacy of Carvedilol

Abstract

Beta-adrenergic receptor (β-AR) blockers are proven therapeutic agents in diverse cardiovascular diseases including hypertension, angina, myocardial infarction and arrhythmias. Recent trials in heart failure patients (MOCHA, PRECISE, ANZ-carvedilol trial, CIBIS I/II, MERIT) have demonstrated the efficacy of β-AR blockers to reduce morbidity and mortality in all grades of heart failure patients, leading to approval of at least one agent, carvedilol, for treatment of this progressive and malignant disease. In this review, the pharmacology of carvedilol is summarised and analysed with particular reference to the mechanism of cardiac protection. Such analysis is critical for understanding the complex mechanisms of carvedilol actions consisting of: 1. non-selective β-AR blocking action; 2. α1-AR blocking action; 3. antioxidant action; 4. prevention of organ remodeling via modulation of gene expression, including apoptosis. The overall combination of carvedilol pharmacology differentiates this drug from any other β-AR blocking agent. In this brief review the pre-clinical pharmacology of carvedilol pertaining to cardioprotection is presented in the context of its potent anti-ischemic properties, its capacity to prevent cardiac remodeling and its potential role in prevention of apoptosis.