Beta-adrenergic blocking agents: past, present, and future perspectives

The 'proof of concept' of beta-blockade for heart failure (i.e. that the pharmacologic actions of beta-blockers are beneficial) is now firmly established, as the treatment of heart failure has progressed from using positive inotropic stimulation, via drugs with no direct effect on cardiac function, to beta-blockers with negative intropic effects. This review addresses some remaining issues regarding beta-blockade in heart failure. The mechanism of action of beta-blockers in heart failure is more likely to be improved intrinsic cardiac myocyte function and prevention or reversal of remodeling, than restoration of beta-adrenergic signal transduction. The role of the differentiating characteristics of beta-blockers is not clear at this time, and there is no compelling evidence to select one agent over another on the basis of individual drug properties. Recent reports suggest that beta-blockers reduce the combined risk of all-cause mortality and hospitalizations by about 30-35%. These results are heavily influenced by experience with carvedilol, but other agents tested include metoprolol, bucindolol, bisoprolol, and nebivolol. Responsiveness to beta-blockers is not related to patients' age, sex, or race, or to the etiology or severity of heart failure. Beta-blockers are currently recommended as adjunctive treatment in patients who remain mildly to moderately symptomatic while receiving added digitalis, diuretics, and angiotensin-converting enzyme inhibitors. Existing gaps in our knowledge must be filled in order to achieve optimal clinical application of beta-blockers. Ongoing studies will provide much of the information required. The role of beta-blockers will probably expand as we improve our understanding of the pathophysiology of heart failure, and especially of the remodeling process.