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Beta-Blocker Therapy for Chronic Heart Failure



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Am Fam Physician. 2003 Apr 15;67(8):1793-1794.

Beta blockers have become standard therapy in patients with chronic heart failure resulting from systolic dysfunction. Kukin reviewed clinical efficacy and mortality trials of beta blockers, as well as factors to consider when prescribing these drugs.

Treatment with beta blockers should be initiated in patients who are stable and euvolemic and do not have a contraindication to their use. These drugs should be titrated slowly to the target dosage or the maximum tolerated dosage. If patients cannot tolerate titration, low-dose beta-blocker therapy should be continued because clinical benefits occur even with smaller amounts.

Adverse effects of beta blockers include hypotension, fluid retention, bradycardia, and heart block. Hypotension typically is short-lived; one solution to this problem is short-term dosage reduction of angiotensin-converting enzyme inhibitors in patients who also use those medications. Fluid retention may require an increased dosage of diuretic. Most patients with bradycardia or heart block are asymptomatic; however, dosage reduction or discontinuation of beta blockers is required if second- or third-degree heart block develops. Tapering the dosage is important because abrupt discontinuation of beta-blocker therapy may elicit coronary insufficiency.

Summary of Major Mortality Trials Evaluating Beta Blockers in Patients with Heart Failure

Annual mortality rate (%)
Beta blocker Number of patients NYHA class LVEF (%) Annual RR vs. placebo in all- cause mortality (%) Beta blocker Placebo

ER metoprolol succinate

3,991

II-IV

40

34

7.2

11.0

Bisoprolol

2,647

III-IV

35

34

11.8

17.3

Bucindolol

2,708

III-IV

35

*

15.0

17.0

Carvedilol

2,289

III-IV

25

35

11.4

18.5


NYHA = New York Heart Association; LVEF = left ventricular ejection fraction; RR = risk reduction; ER = extended release.

*—RR for total mortality, 10 percent (33 percent placebo, 30.2 percent bucindolol).

Adapted with permission from Kukin ML. β-blockers in chronic heart failure: considerations for selecting an agent. Mayo Clin Proc 2002;77:1200.

Summary of Major Mortality Trials Evaluating Beta Blockers in Patients with Heart Failure

View Table

Summary of Major Mortality Trials Evaluating Beta Blockers in Patients with Heart Failure

Annual mortality rate (%)
Beta blocker Number of patients NYHA class LVEF (%) Annual RR vs. placebo in all- cause mortality (%) Beta blocker Placebo

ER metoprolol succinate

3,991

II-IV

40

34

7.2

11.0

Bisoprolol

2,647

III-IV

35

34

11.8

17.3

Bucindolol

2,708

III-IV

35

*

15.0

17.0

Carvedilol

2,289

III-IV

25

35

11.4

18.5


NYHA = New York Heart Association; LVEF = left ventricular ejection fraction; RR = risk reduction; ER = extended release.

*—RR for total mortality, 10 percent (33 percent placebo, 30.2 percent bucindolol).

Adapted with permission from Kukin ML. β-blockers in chronic heart failure: considerations for selecting an agent. Mayo Clin Proc 2002;77:1200.

The U.S. Food and Drug Administration has labeled only extended-release metoprolol succinate and carvedilol for the treatment of chronic heart failure. Metoprolol is beta1 selective, and carvedilol is nonselective. Extended-release metoprolol succinate can be started in a dosage of 25 mg per day in patients with New York Heart Association class II failure; in patients with more severe heart failure, the starting dosage should be 12.5 mg per day. The recommended starting dosage of carvedilol is 3.125 mg twice daily. The mortality benefits of metoprolol have been proved only for the extended-release form. The theoretic benefits of nonselective agents such as carvedilol have not translated into a mortality benefit over beta1-selective agents in currently available trials. A number of major trials have evaluated the mortality benefits of beta blockers in patients with chronic heart failure (see accompanying table).

While there may be individual benefits with either drug, to date, no large-scale studies have directly compared mortality with the use of extended-release metoprolol succinate versus carvedilol. The author concluded that no data support the choice of one agent over the other.

Kukin ML. β-Blockers in chronic heart failure: considerations for selecting an agent. Mayo Clin Proc. November 2002;77:1199–206.

editor’s note: The mortality benefit of beta-blocker therapy in patients with chronic heart failure is clear. Studies continue to show less than ideal use of these medications in patients with chronic heart failure. Current expert guidelines recommend the use of beta blockers in all stable patients who have evidence of left ventricular systolic dysfunction (generally defined as an ejection fraction of less than 40 percent), unless there is a contraindication to their use.A European trial comparing metoprolol and carvedilol is nearing completion, but it does not compare the extended-release form of metoprolol with carvedilol.—c.c.

 

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