Metoprolol, a relatively selective beta1-blocker, is devoid of intrinsic
sympathomimetic activity and possesses weak membrane stabilising activity. The
drug has an established role in the management of
essential hypertension and
angina pectoris, and more recently, in patients with chronic
heart failure. The effects of
metoprolol controlled-release/extended-release (CR/XL) in patients with stable, predominantly mild to moderate (NYHA functional class II to III) chronic
heart failure have been evaluated in the large
Metoprolol CR/XL Randomised Intervention Trial in
Congestive Heart Failure (MERIT-HF) trial and the much smaller Randomized Evaluation of Strategies for
Left Ventricular Dysfunction (RESOLVD) pilot study. Treatment with
metoprolol CR/XL was initiated at a low dosage of 12.5 to 25 mg once daily and gradually increased at 2-weekly intervals until the target dosage (200 mg once daily) or maximal tolerated dosage had been attained in patients receiving standard
therapy for
heart failure. At 12 months,
metoprolol CR/XL was associated with a 34% reduction in relative risk of all-cause mortality in patients with chronic
heart failure due to ischaemic or
dilated cardiomyopathy in the MERIT-HF trial. The incidence of
sudden death and death due to progressive
heart failure were both significantly decreased with
metoprolol CR/XL. Similarly, a trend towards decreased mortality in the
metoprolol CR/XL group compared with placebo was observed in the RESOLVD trial. Data from small numbers of patients with severe (NYHA functional class IV)
heart failure indicate that
metoprolol CR/XL is effective in this subset of patients. However, no firm conclusions can yet be drawn. Improvement from baseline values in NYHA functional class, exercise capacity and some measures of quality of life with
metoprolol CR/XL or immediate-release
metoprolol were significantly greater than those with placebo. The
drug is well tolerated when treatment is initiated in low dosages and gradually increased at intervals of 1 to 2 weeks.
CONCLUSIONS: