Neurohumoral Mechanisms in Congestive Heart Failure and the Role of Drugs with Multiple Actions: A Review of Carvedilol.

Treatments based on mechanistic models of heart failure, although entirely rational, have not succeeded in reducing mortality. A more holistic view, based on the concept that the neurohumoral environment is a common factor, encompasses all the previous theoretical models and extends them to provide a new approach to treatment. Vasodilators, inotropes, and angiotensin-converting enzyme (ACE) inhibitors all modify hemodynamics favorably and improve cardiac-performance. Only the vasodilators and ACE inhibitors have been shown to reduce morbidity and mortality. With the ACE inhibitors, this effect is related to changes in the levels of circulating angiotensin II and noradrenaline rather than to improved hemodynamics. There is direct evidence that adrenergic receptor density is reduced in chronic heart failure. Vasodilating beta-blockers, like carvedilol, that suppress adrenergic overactivity and reduce preload and afterload, offer a new approach to treatment, but the exploitation of this new opportunity is inhibited by the widely held belief that beta-blockers should be avoided in heart failure. This mistaken view is based on the experience of beta-blockers in angina pectoris and after myocardial infarction, experience that should not exclude their use in patients with congestive heart failure. Vasodilating beta-blockers, introduced at an appropriate dosage, may have an important role to play in the overall management of congestive failure.