title: Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF). MERIT-HF Study Group.
abstract: BACKGROUND
  Results from recent studies on the effects of beta1-blockade in patients with heart failure demonstrated a 34% reduction in total mortality. However, the effect of beta1-blockade on the frequency of hospitalizations, symptoms, and quality of life in patients with heart failure has not been fully explored.
  
  
  OBJECTIVE
  To examine the effects of the beta1-blocker controlled-release/extended-release metoprolol succinate (metoprolol CR/XL) on mortality, hospitalization, symptoms, and quality of life in patients with heart failure.
  
  
  METHODS
  Randomized, double-blind controlled trial, preceded by a 2-week single-blind placebo run-in period, conducted from February 14, 1997, to October 31, 1998, with a mean follow-up of 1 year.
  
  
  METHODS
  Three hundred thirteen sites in 14 countries.
  
  
  METHODS
  Patients (n = 3991) with chronic heart failure, New York Heart Association (NYHA) functional class II to IV, and ejection fraction of 0.40 or less who were stabilized with optimum standard therapy.
  
  
  METHODS
  Patients were randomized to metoprolol CR/XL, 25 mg once per day (NYHA class II), or 12.5 mg once per day (NYHA class III or IV), titrated for 6 to 8 weeks up to a target dosage of 200 mg once per day (n = 1990); or matching placebo (n = 2001).
  
  
  METHODS
  Total mortality or any hospitalization (time to first event), number of hospitalizations for worsening heart failure, and change in NYHA class, by intervention group; quality of life was assessed in a substudy of 741 patients.
  
  
  RESULTS
  The incidence of all predefined end points was lower in the metoprolol CR/XL group than in the placebo group, including total mortality or all-cause hospitalizations (the prespecified second primary end point; 641 vs 767 events; risk reduction, 19%; 95% confidence interval [CI], 10%-27%; P<.001); total mortality or hospitalizations due to worsening heart failure (311 vs 439 events; risk reduction, 31%; 95% CI, 20%-40%; P<.001), number of hospitalizations due to worsening heart failure (317 vs 451; P<.001); and number of days in hospital due to worsening heart failure (3401 vs 5303 days; P<.001). NYHA functional class, assessed by physicians, and McMaster Overall Treatment Evaluation score, assessed by patients, both improved in the metoprolol CR/XL group compared with the placebo group (P = .003 and P = .009, respectively).
  
  
  CONCLUSIONS
  In this study of patients with symptomatic heartfailure, metoprolol CR/XL improved survival, reduced the need for hospitalizations due to worsening heart failure, improved NYHA functional class, and had beneficial effects on patient well-being.
authors.affiliation: Department of Cardiology, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Hjalmarson
authors.forename: S
authors.initials: S
authors.lastname: Goldstein
authors.forename: B
authors.initials: B
authors.lastname: Fagerberg
authors.forename: H
authors.initials: H
authors.lastname: Wedel
authors.forename: F
authors.initials: F
authors.lastname: Waagstein
authors.forename: J
authors.initials: J
authors.lastname: Kjekshus
authors.forename: J
authors.initials: J
authors.lastname: Wikstrand
authors.forename: D
authors.initials: D
authors.lastname: El Allaf
authors.forename: J
authors.initials: J
authors.lastname: Vítovec
authors.forename: J
authors.initials: J
authors.lastname: Aldershvile
authors.forename: M
authors.initials: M
authors.lastname: Halinen
authors.forename: R
authors.initials: R
authors.lastname: Dietz
authors.forename: K L
authors.initials: KL
authors.lastname: Neuhaus
authors.forename: A
authors.initials: A
authors.lastname: Jánosi
authors.forename: G
authors.initials: G
authors.lastname: Thorgeirsson
authors.forename: P H
authors.initials: PH
authors.lastname: Dunselman
authors.forename: L
authors.initials: L
authors.lastname: Gullestad
authors.forename: J
authors.initials: J
authors.lastname: Kuch
authors.forename: J
authors.initials: J
authors.lastname: Herlitz
authors.forename: P
authors.initials: P
authors.lastname: Rickenbacher
authors.forename: S
authors.initials: S
authors.lastname: Ball
authors.forename: S
authors.initials: S
authors.lastname: Gottlieb
authors.forename: P
authors.initials: P
authors.lastname: Deedwania
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D016016:Proportional Hazards Models; D011788:Quality of Life; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D003692:Delayed-Action Preparations; D008790:Metoprolol