[New and old beta-blockers in the treatment of heart failure]

Controlled clinical trials, performed in more than 16,000 patients to date, have consistently shown the beneficial effects of long-term beta-blocker therapy in patients with chronic heart failure. However, it is not clear whether this represents a class effect or it is specific only to some agents. Beneficial effects on the prognosis of the patients with mild to moderate heart failure have been shown with metoprolol, bisoprolol, and carvedilol. However, these beta-blockers differ in their pharmacological characteristics. Metoprolol and bisoprolol are selective for beta 1-adrenergic receptors and are devoid of ancillary properties. Carvediol, at doses of 50 mg daily, blocks all beta 1-, beta 2-, and alpha 1- adrenergic receptors, and has associated antiproliferative and antioxidant activities. These differences cause a different acute hemodynamic response with a reduction in cardiac output and a tendency to a rise in pulmonary wedge pressure with selective agents and no change in cardiac output and a slight decrease in pulmonary pressures with carvedilol. Accordingly, when the therapy is started, the most frequent side effects are worsening heart failure with metoprolol and bisoprolol and hypotension and dizziness with carvedilol. It is still controversial whether these differences may also influence the long-term effects of therapy. Differently from selective beta-blockers, carvedilol does not upregulate beta 1-receptors, blocks all adrenergic receptors, decreases cardiac norepinephrine release, thus providing a more comprehensive blockade of the cardiac adrenergic drive. These properties have caused a larger increase in LV function and a lack of improvement in maximal exercise capacity with carvedilol, compared to selective beta-blockers. It is however, unclear whether these differences may also influence the patients' outcome.