Beta-blocking agents are now being used routinely to treat patients with New York Heart Association (NYHA) classes II and III systolic chronic heart failure. Efficacy and safety in more severely ill patients, those with NYHA class IV congestive heart failure (CHF), are less clear.

Whorlow and Krum conducted a meta-analysis of all published placebo-controlled studies in which beta blockers were given to NYHA class IV patients with follow-up measurement of mortality outcomes. Additional inclusion criteria included objective documentation of systolic CHF, the administration of beta blockers for at least three months, symptoms documented at baseline and subsequent mortality outcomes recorded. Among the four studies that included patients who were known to have NYHA class IV symptoms at baseline, the overall relative risk benefit of beta blockade versus placebo was 0.71, with a 95 percent confidence interval of 0.52 to 0.96.

There has been some concern about beta blockade in patients with severe CHF because of the dependence on increased sympathetic drive to maintain cardiac performance. Surprisingly, these patients seem to benefit from beta blockade, assuming that their volume status has been optimized when therapy is begun.

The authors conclude that the 29 percent relative risk reduction seen in these class IV CHF patients with beta blockade compares favorably with the overall 32 percent relative risk among all patients with symptomatic heart failure. There appears to be no difference in the efficacy of either of the drugs most extensively studied, metoprolol and bisoprolol. Questions about drug tolerability in patients with NYHA class IV CHF symptoms remain. The decision to initiate beta-blocker therapy in patients with class IV CHF involves an evaluation of the overall benefits versus the risks of treatment. More information will be available about beta blockade in this group of patients with the completion of prospective large-scale mortality studies.

editor's note: Chronic congestive heart failure is associated with activation of the sympathetic nervous system hemodynamically supporting the weakening myocardium. Over long periods of time, this activation may be harmful, since excess catecholamines appear to contribute to disease progression and increased mortality. Blocking sympathetic activation is a reasonable approach to managing systolic congestive heart failure. Beta blockers that block the cardiac effects of sympathetic activation are associated with improved long-term functional and mortality outcomes. Nonselective beta-adrenergic blocking drugs appear to be most effective. Carvedilol and metoprolol are two formulations that have been extensively used in the United States. Patients should be started on subtherapeutic dosages and titrated upward. Most studies have confirmed the value of beta blockers in NYHA classes II and III patients, with newer studies demonstrating value in NYHA class IV patients and in patients with asymptomatic left ventricular dysfunction.—r.s.