Current Role of Beta-Adrenergic Blockers
Current Role of Beta-Adrenergic Blockers
Recent findings on the use of ß-adrenergic blockers in patients with congestive heart failure (CHF) are reviewed.
CHF is a progressive, debilitating disease that afflicts 4.6 million patients in the United States. Treatment has traditionally consisted of a diuretic, an angiotensin-converting- enzyme (ACE) inhibitor, and digoxin. Despite advances in ACE-inhibitor therapy, the five-year mortality rate remains nearly 50%. Overstimulation of the sympathetic nervous system is believed to contribute to mortality. Beta-blockers have recently been added to the standard of care for patients with New York Heart Association functional class II or III heart failure. Four randomized, double-blind, placebo-controlled clinical trials were recently completed that addressed the benefits of ß-blockers in CHF. The overall mortality rate was reduced 65% by carvedilol, 34% by metoprolol, and 33% by bisoprolol; all these reductions were significant compared with placebo, and the trials were ended early. Bucindolol, however, did not have a significant effect on mortality. These drugs are hepatically metabolized and may require dosage adjustment in hepatically impaired patients. Decompensation of heart failure is another consideration; a ß-blocker should be added only for patients with stable CHF. Dosages must be slowly adjusted to targeted levels. Adverse effects do not differ significantly among ß-blockers. In addition to their effect on mortality, ß-blockers reduce CHF-related morbidity, such as all-cause hospitalization.
Carvedilol, metoprolol, and bisoprolol decrease the mortality and morbidity associated with CHF and can be used with limited adverse effects. The choice among these agents does not affect clinical outcomes; bucindolol, however, has proven ineffective.
Congestive heart failure (CHF) is a progressive, debilitating disease that afflicts 4.6 million patients in the United States. The prevalence is 10 per 1000 in patients older than 65 years, and 550,000 new cases are diagnosed annually. CHF cost the United States an estimated $22.5 billion in direct and indirect costs in 1999. The disease is characterized by dyspnea, fatigue, and peripheral edema resulting from a decrease in the left ventricle's ability to eject blood. Symptom severity is often rated by New York Heart Association functional class (NYHA-FC), in which class I represents a patient with no limitations and class IV a patient with symptoms even at rest.
Treatment of CHF has traditionally consisted of a diuretic, an angiotensin-converting- enzyme (ACE) inhibitor, and digoxin. A meta-analysis of ACE-inhibtor trials in CHF has shown that these agents decrease mortality by 23%. However, despite advances in therapy with ACE inhibitors, the five-year mortality rate for CHF remains nearly 50%. Overstimulation of the sympathetic nervous system in CHF patients is thought to contribute to mortality. The increased level of circulating norepinephrine has many detrimental effects. Norepinephrine can induce cardiac remodeling (enlargement) either directly or indirectly through stimulation of the renin-angiotensin-aldosterone system (RAAS). Excess levels of norepinephrine are directly toxic to cardiac myocytes. Salt and water retention is also stimulated by increased activity of the RAAS.
Blockade of ß-adrenergic receptors with drugs inhibits the deleterious effects of the overstimulated sympathetic nervous system. This forms the theoretical basis of using ß-adrenergic blockers to treat CHF. Currently, carvedilol is the only ß-blocker whose labeling includes an indication for the treatment of CHF. Three other ß-blockers have also been intensively studied in CHF: metoprolol, 6-9 bisoprolol, and bucindolol.
This article reviews the current literature on the use of ß-blockers in CHF and explores whether the data support the selection of one ß-blocker over another.
Recent findings on the use of ß-adrenergic blockers in patients with congestive heart failure (CHF) are reviewed.
CHF is a progressive, debilitating disease that afflicts 4.6 million patients in the United States. Treatment has traditionally consisted of a diuretic, an angiotensin-converting- enzyme (ACE) inhibitor, and digoxin. Despite advances in ACE-inhibitor therapy, the five-year mortality rate remains nearly 50%. Overstimulation of the sympathetic nervous system is believed to contribute to mortality. Beta-blockers have recently been added to the standard of care for patients with New York Heart Association functional class II or III heart failure. Four randomized, double-blind, placebo-controlled clinical trials were recently completed that addressed the benefits of ß-blockers in CHF. The overall mortality rate was reduced 65% by carvedilol, 34% by metoprolol, and 33% by bisoprolol; all these reductions were significant compared with placebo, and the trials were ended early. Bucindolol, however, did not have a significant effect on mortality. These drugs are hepatically metabolized and may require dosage adjustment in hepatically impaired patients. Decompensation of heart failure is another consideration; a ß-blocker should be added only for patients with stable CHF. Dosages must be slowly adjusted to targeted levels. Adverse effects do not differ significantly among ß-blockers. In addition to their effect on mortality, ß-blockers reduce CHF-related morbidity, such as all-cause hospitalization.
Carvedilol, metoprolol, and bisoprolol decrease the mortality and morbidity associated with CHF and can be used with limited adverse effects. The choice among these agents does not affect clinical outcomes; bucindolol, however, has proven ineffective.
Congestive heart failure (CHF) is a progressive, debilitating disease that afflicts 4.6 million patients in the United States. The prevalence is 10 per 1000 in patients older than 65 years, and 550,000 new cases are diagnosed annually. CHF cost the United States an estimated $22.5 billion in direct and indirect costs in 1999. The disease is characterized by dyspnea, fatigue, and peripheral edema resulting from a decrease in the left ventricle's ability to eject blood. Symptom severity is often rated by New York Heart Association functional class (NYHA-FC), in which class I represents a patient with no limitations and class IV a patient with symptoms even at rest.
Treatment of CHF has traditionally consisted of a diuretic, an angiotensin-converting- enzyme (ACE) inhibitor, and digoxin. A meta-analysis of ACE-inhibtor trials in CHF has shown that these agents decrease mortality by 23%. However, despite advances in therapy with ACE inhibitors, the five-year mortality rate for CHF remains nearly 50%. Overstimulation of the sympathetic nervous system in CHF patients is thought to contribute to mortality. The increased level of circulating norepinephrine has many detrimental effects. Norepinephrine can induce cardiac remodeling (enlargement) either directly or indirectly through stimulation of the renin-angiotensin-aldosterone system (RAAS). Excess levels of norepinephrine are directly toxic to cardiac myocytes. Salt and water retention is also stimulated by increased activity of the RAAS.
Blockade of ß-adrenergic receptors with drugs inhibits the deleterious effects of the overstimulated sympathetic nervous system. This forms the theoretical basis of using ß-adrenergic blockers to treat CHF. Currently, carvedilol is the only ß-blocker whose labeling includes an indication for the treatment of CHF. Three other ß-blockers have also been intensively studied in CHF: metoprolol, 6-9 bisoprolol, and bucindolol.
This article reviews the current literature on the use of ß-blockers in CHF and explores whether the data support the selection of one ß-blocker over another.
