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Am Fam Physician. 1999;59(6):1663

Although beta-blocking medications have been demonstrated to improve left ventricular function and morbidity in patients with heart failure, concerns about safety and the overall effect on mortality have limited the routine use of these agents. Meta-analysis of several clinical trials has shown an estimated reduction in mortality of about 30 percent. A large European multicenter trial reports on the effect of beta blockade on rates of mortality in patients with heart failure.

The Cardiac Insufficiency Bisoprolol Study group included over 100 investigators in 20 countries, and 2,647 symptomatic patients with heart failure were enrolled. Patients were 18 to 80 years of age with symptoms consistent with New York Heart Association (NYHA) class III or IV heart failure and left ventricular ejection fractions of 35 percent or less. All patients had been diagnosed at least three months previously. Treatment was required to include diuretics and angiotensin converting enzyme (ACE) inhibitors, although use of digoxin and other medications was optional. Patients were randomly assigned to receive 1.25 mg of bisoprolol or an identical placebo daily. The dosage was gradually increased to 10 mg daily as tolerated. Patients were monitored every three months by study personnel.

The study was stopped early because the mortality rate in the bisoprolol patients was significantly less than that in patients receiving placebo. The mean follow-up time was 1.3 years. During this period, 156 treated patients (11.8 percent) died, compared with 228 patients in the placebo group (17.3 percent). Patients receiving bisoprolol were significantly less likely to die from or be admitted to the hospital for a cardiovascular event. These differences were maintained when data were analyzed by cause and severity of heart failure. The incidence of sudden death was reduced by 42 percent in patients receiving bisoprolol (48 sudden deaths compared with 83 in the placebo group). Hospital admission for deteriorating heart failure was reduced by 32 percent (159 patients in the treatment group compared with 232 in the placebo group). Admissions were also significantly reduced for ventricular tachycardia, ventricular fibrillation and hypotension but were increased for stroke, although the increase was not significant.

The authors conclude that beta blockade has a significant benefit in patients with NYHA class III and IV heart failure. These findings confirm the benefit projected from meta-analyses and other studies. They recommend that beta blockers be added to standard therapeutic regimens of diuretics and ACE inhibitors in patients with stable heart failure. Since much remains to be elucidated about the optimal use of these combinations of treatments, they recommend starting with a low dosage of a beta blocker and progressively increasing to the maximum tolerated dosage. In this study, 10 mg daily was the most common maintenance dosage.

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