Extended-release metoprolol succinate in chronic heart failure

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and tolerability of extended-release (ER) metoprolol succinate and its role in the management of chronic heart failure. DATA SOURCES: A MEDLINE search of English-language literature (1990-October 2002) was conducted using congestive heart failure and metoprolol CR/XL or metoprolol CR/ZOK as search terms to identify pertinent studies. STUDY SELECTION/DATA EXTRACTION: All of the articles identified from the data sources were evaluated, with priority given to randomized, double-blind, placebo-controlled studies. DATA SYNTHESIS: ER metoprolol succinate is a controlled-release tablet designed to produce even and consistent beta(1)-blockade throughout the 24-hour dosing interval, with less fluctuation in metoprolol plasma concentrations compared with immediate-release metoprolol. Three randomized, double-blind, placebo-controlled trials have evaluated the efficacy of ER metoprolol succinate in the treatment of patients with chronic heart failure. The MERIT-HF (Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure) study, the largest of these trials and the largest randomized mortality trial with beta-blockers in heart failure to date, demonstrated that ER metoprolol succinate reduced the relative risk of all-cause mortality by 34% versus placebo. Furthermore, the relative risk of the combined endpoint of mortality plus all-cause hospitalizations was reduced by 19% and sudden death was reduced by 41%. The benefits of therapy were evident in various patient subgroups, including elderly patients and those with diabetes mellitus. ER metoprolol succinate was generally well tolerated, with a similar proportion of patients discontinuing therapy due to adverse events relative to placebo (9.8% and 11.7%, respectively). CONCLUSIONS: ER metoprolol succinate therapy provides substantial mortality and morbidity benefits in patients with New York Heart Association class II and III heart failure who are stabilized on angiotensin-converting enzyme inhibitors and diuretics. ER metoprolol succinate is administered once daily, is well tolerated, and provides consistent beta(1)-blockade over the 24-hour dosing interval.