title: Sustained restoration of autonomic balance with long- but not short-acting metoprolol in patients with heart failure.
abstract: BACKGROUND
  The purpose of this study was to compare the effects of immediate-release (IR) metoprolol and extended-release (XL) metoprolol on measures of heart rate variability in chronic systolic heart failure patients.
  
  
  RESULTS
  Thirteen metoprolol-treated heart failure patients were randomized to a 2-way crossover study of equal daily doses of metoprolol IR and metoprolol XL, each administered for 3 weeks. After each 3-week interval, patients underwent 24-hour Holter and ambulatory blood pressure monitoring. Over the entire 24-hour period, the ratio of high to total variability (normalized measure of parasympathetic activity) was significantly greater (P < .05), the ratio of low to total variability (normalized measure of sympathetic activity) was significantly lower (P < .05), and the ratio of high to low variability (index of parasympathetic to sympathetic balance) was greater (P < .08) for metoprolol XL compared with metoprolol IR. Over the entire 24-hour period, both systolic and diastolic blood pressure were significantly lower for metoprolol XL compared with metoprolol IR (P < .0001, and .0005, respectively).
  
  
  CONCLUSIONS
  These data suggest that with twice daily dosing, metoprolol IR is inferior to metoprolol XL in its effects on heart rate variability, autonomic balance, and blood pressure in patients with heart failure.
authors.affiliation: Department of Pharmacy Practice, University of Florida College of Pharmacy, Gainesville, 32610, USA.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Aquilante
authors.forename: Steven G
authors.initials: SG
authors.lastname: Terra
authors.forename: Richard S
authors.initials: RS
authors.lastname: Schofield
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Pauly
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Hatton
authors.forename: Philip F
authors.initials: PF
authors.lastname: Binkley
authors.forename: Julie A
authors.initials: JA
authors.lastname: Johnson
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000368:Aged; D001341:Autonomic Nervous System / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008875:Middle Aged; D013997:Time Factors
chemical_list: D000319:Adrenergic beta-Antagonists; D003692:Delayed-Action Preparations; D008790:Metoprolol