Critical differences among beta-adrenoreceptor antagonists in myocardial failure: debating the MERIT of COMET

In the United States, carvedilol and metoprolol (tartrate or succinate) are the most commonly employed beta-adrenoreceptor antagonists for the treatment of heart failure. However, use of these agents in patients with heart failure remains extremely low despite overwhelming evidence of their beneficial short- and long-term effects. Because the myocardial pathophysiology associated with heart failure involves not only beta-1 adrenoreceptors but also beta-2 and alpha-1 adrenoreceptors, this indicates a more complex disease process that may require pan-receptor antagonism to provide optimal clinical benefit. Relative to metoprolol (tartrate or succinate), carvedilol represents an extremely complex molecular entity that not only possesses the ability to antagonize all of the principle adrenoreceptors involved in heart failure but also reduces oxidative stress and provides an antiarrhythmic benefit independent of beta-adrenoreceptor antagonism. Taken together, an interesting pharmacologic premise for the superiority of carvedilol relative to metoprolol (tartrate) may exist, but the lack of clinical trials comparing an optimal dose of either extended-release metoprolol (ie, succinate) or immediate-release metoprolol (ie, tartrate) to carvedilol limits the clinical application of the pharmacologic differences between the agents.