title: Metoprolol CR/XL in patients with heart failure: A pilot study examining the tolerability, safety, and effect on left ventricular ejection fraction.
abstract: BACKGROUND
  This study was designed to investigate the tolerability, safety, and effect on left ventricular function of a new long-acting preparation of metoprolol, metoprolol succinate (CR/XL).
  
  
  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 metoprolol succinate and placebo groups, respectively. The drug was well tolerated and there was no significant difference in drug withdrawals, New York Heart Association class, or quality of life assessment. The increase in left ventricular ejection fraction measure at baseline and 6 months measured by radioisotopic ventriculography was greater in the metoprolol succinate group (27. 5% to 36.3%) than in the placebo group (26% to 27.9%) (P <.015). Examination of serial Holter electrocardiographic recordings indicate that metoprolol succinate therapy was associated with a significant (P <.05) decrease in total ventricular ectopy at 8 weeks of therapy and a decrease in ventricular couplets and nonsustained ventricular tachycardia at 8 through 26 weeks of therapy. No changes were observed in plasma norepinephrine during therapy except a transitory significant (P <.05) increase in N terminal proatrial natriuretic factor at 8 weeks in the metoprolol succinate group.
  
  
  CONCLUSIONS
  This study indicates that treatment with metoprolol succinate for a 6-month period is safe and well tolerated and is associated with an increase in left ventricular ejection fraction and a decrease in ventricular ectopic beats.
authors.affiliation: Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, MI 48202, USA.
authors.forename: S
authors.initials: S
authors.lastname: Goldstein
authors.forename: H L
authors.initials: HL
authors.lastname: Kennedy
authors.forename: C
authors.initials: C
authors.lastname: Hall
authors.forename: J L
authors.initials: JL
authors.lastname: Anderson
authors.forename: M
authors.initials: M
authors.lastname: Gheorghiade
authors.forename: S
authors.initials: S
authors.lastname: Gottlieb
authors.forename: M
authors.initials: M
authors.lastname: Jessup
authors.forename: R P
authors.initials: RP
authors.lastname: Karlsberg
authors.forename: G
authors.initials: G
authors.lastname: Friday
authors.forename: L
authors.initials: L
authors.lastname: Haskell
mesh_terms: D004311:Double-Blind Method; D015716:Electrocardiography, Ambulatory; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D010865:Pilot Projects; D013318:Stroke Volume / Q000187:drug effects*
chemical_list: D008790:Metoprolol