Use of multiple-action agents on the heart: pathophysiological and therapeutic considerations

The introduction of beta-adrenoreceptor antagonists into clinical practice has resulted in major progress in the treatment of hypertension, angina pectoris, and congestive heart failure. However, the first and second (beta 1 selective) generations of beta-blockers induce a series of unwanted functional and metabolic effects, suggesting the search for a third generation of beta-antagonists. The new multiple-action beta-blockers, which have important peripheral vasodilator properties, appear to be promising with regard to clinical efficacy and side effects. In hypertensive patients, the vasodilation could add a more pathophysiological mechanism and therefore could induce a better preservation of systolic function. The global cardioprotection may be further improved by the absence of long-term metabolic effects. By virtue of their peripheral and coronary vasodilating properties, multiple-action beta-blockers could exert more favorable anti-ischemic effects in patients with angina pectoris than the traditional beta-blockers. In congestive heart failure, afterload reduction, and possibly myocardial beta 2-activation induced by multiple-action beta-blockers can minimize the negative inotropic effects, leading to better toleration at the beginning of treatment. The potential benefits of multiple-action beta-blockers have been assessed by preliminary studies and should be confirmed by trials in progress.