Metoprolol: a review of its use in chronic heart failure

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: Metoprolol CR/XL effectively decreases mortality and improves clinical status in patients with stable mild to moderate (NYHA functional class II or III) chronic heart failure due to left ventricular systolic dysfunction, and the drug is effective in patients with ischaemic or dilated cardiomyopathy. Although limited data indicate that metoprolol CR/XL is effective in patients with severe (NYHA functional class IV) chronic heart failure, more data are needed to confirm these findings. Treatment with metoprolol CR/XL significantly reduced the incidence of sudden death and death due to progressive heart failure.