title: Controlled release metoprolol for aortic regurgitation: a randomised clinical trial.
abstract: OBJECTIVE
  Chronic aortic regurgitation (AR) creates a volume load on the left ventricle, which induces adaptive responses. With time, excessive left ventricular (LV) dilatation may precipitate heart failure. β-adrenergic receptor antagonists (β-blockers) are beneficial in patients with heart failure, but their effect in AR is unclear. This trial was designed to evaluate the effect of controlled release metoprolol on LV remodelling in patients with AR.
  
  
  METHODS
  In this double blind trial, 75 asymptomatic patients aged 44±14 years, 89% males, fulfilling at least two echocardiographic criteria for moderate or severe chronic AR, were randomised to receive metoprolol CR/XL up-titrated to 200 mg/day, or matching placebo. The primary endpoint was LV end diastolic volume, measured by MRI after 6 months of treatment.
  
  
  RESULTS
  After 6 months, the difference in the baseline-adjusted LV end diastolic volume between patients allocated to metoprolol and those allocated to placebo was 8 (95% CI -8 to 25) mL (p=0.32). The adjusted LV ejection fraction was 2.7 (95% CI 0.1 to 5.3) percentage points higher in the metoprolol group than in the placebo group (p=0.04). The exercise capacity and peak oxygen consumption did not differ between treatment arms. Serum concentrations of N-terminal pro-B-type natriuretic peptide were 138 (95% CI 71 to 205) pg/mL higher in the metoprolol group (p<0.001). There were no serious adverse events in either treatment arm.
  
  
  CONCLUSIONS
  Treatment with metoprolol of adults with chronic, moderate to severe AR had no effect on LV volumes.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT01157572-results.
authors.affiliation: Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway Faculty of Medicine, K. G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, University of Oslo, Oslo, Norway.
authors.forename: Kaspar
authors.initials: K
authors.lastname: Broch
authors.affiliation: Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway Institute for Surgical Research, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Stig
authors.initials: S
authors.lastname: Urheim
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.
authors.forename: Mai Tone
authors.initials: MT
authors.lastname: Lønnebakken
authors.affiliation: Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Wenche
authors.initials: W
authors.lastname: Stueflotten
authors.affiliation: Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Richard
authors.initials: R
authors.lastname: Massey
authors.affiliation: Department of Radiology and Nuclear Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Kristian
authors.initials: K
authors.lastname: Fosså
authors.affiliation: Department of Radiology and Nuclear Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Einar
authors.initials: E
authors.lastname: Hopp
authors.affiliation: Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Svend
authors.initials: S
authors.lastname: Aakhus
authors.affiliation: Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway Faculty of Medicine, K. G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, University of Oslo, Oslo, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000627:therapeutic use*; D000328:Adult; D001022:Aortic Valve Insufficiency / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D058070:Asymptomatic Diseases; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005080:Exercise Test; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010101:Oxygen Consumption; D010446:Peptide Fragments / Q000097:blood; D012720:Severity of Illness Index; D016896:Treatment Outcome; D020257:Ventricular Remodeling
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D003692:Delayed-Action Preparations; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D008790:Metoprolol