Metoprolol CR/XL in patients with heart failure: A pilot study examining the tolerability, safety, and effect on left ventricular ejection fraction

Background This study was designed to investigate the tolerability, safety, and effect on left ventricular function of a new long-acting preparation o f metoprolol, metoprolol succinate (CR/XL). Methods and Results Sixty patients were randomly assigned with a 2:1 ratio, drug versus placebo, administered with a gradually increasing dose of 12.5 to 150 mg of blinded medication during an 8-week period and continued for 6 months. The average peak dose achieved was 99 mg and 132 mg in the metopr olol succinate and placebo groups, respectively. The drug was well tolerate d and there was no significant difference in drug withdrawals, New York Hea rt Association class, or quality of life assessment. The increase in left v entricular ejection fraction measure at baseline and 6 months measured by r adioisotopic ventriculography was greater in the metoprolol succinate group (27.5% to 36.3%) than in the placebo group (26% to 27.9%) (P < .015). Exam ination of serial Holter electrocardiographic recordings indicate that meto prolol succinate therapy was associated with a significant (P < .05) decrea se in total ventricular ectopy at 8 weeks of therapy and a decrease in vent ricular couplets and nonsustained ventricular tachycardia at 8 through 26 w eeks of therapy. No changes were observed in plasma norepinephrine during t herapy except a transitory significant (P < .05) increase in N terminal pro atrial natriuretic factor at 8 weeks in the metoprolol succinate group. Conclusions This study indicates that treatment with metoprolol succinate f or a 6-month period is safe and well tolerated and is associated with an in crease in left ventricular ejection fraction and a decrease in ventricular ectopic beats.