Metoprolol - A review of its use in chronic heart failure

Metoprolol, a relatively selective beta(1)-blocker, is devoid of intrinsic sympathomimetic activity and possesses weak membrane stabilising activity. The drug has an established role in the management of essential hypertensio n and angina pectoris, and more recently, in patients with chronic heart fa ilure. The effects of metoprolol controlled-release/extended-release (CR/XL) in pa tients with stable, predominantly mild to moderate (NYHA functional class I I 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 Ve ntricular Dysfunction (RESOLVD) pilot study. Treatment with metoprolol CR/X L was initiated at a low dosage of 12.5 to 25mg once daily and gradually in creased at 2-weekly intervals until the target dosage (200mg 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 relat ive 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 signi ficantly decreased with metoprolol CR/XL. Similarly, a trend towards decrea sed mortality in the metoprolol CR/XL group compared with placebo was obser ved in the RESOLVD trial. Data from small numbers of patients with severe ( NYHA functional class IV) heart failure indicate that metoprolol CR/XL is e ffective in this subset of patients. However, no firm conclusions can yet b e drawn. Improvement from baseline values in NYHA functional class,exercise capacity and some measures of quality of life with metoprolol CR/XL or imm ediate-release metoprolol were significantly greater than those with placeb o. The drug is well tolerated when treatment is initiated in low dosages and g radually 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 c lass II or III) chronic heart failure due to left ventricular systolic dysf unction, and the drug is effective in patients with ischaemic or dilated ca rdiomyopathy. Although Limited data indicate that metoprolol CR/XL is effec tive in patients with severe (NYHA functional class IV) chronic heart failu re, more data are needed to confirm these findings. Treatment with metoprol ol CR/XL significantly reduced the incidence of sudden death and death due to progressive heart failure.