title: A randomised, placebo-controlled trial of carvedilol in early familial dilated cardiomyopathy.
abstract: BACKGROUND
  Screening of asymptomatic relatives of patients with dilated cardiomyopathy (DCM) has identified a population of individuals with left ventricular dilatation and/or minimally impaired contraction who are believed to have early disease. A proportion of these individuals with early disease progress to overt cardiomyopathy, however to our knowledge there have been no studies that have examined the impact of early intervention on disease progression.
  
  
  METHODS
  We evaluated 424 asymptomatic relatives in 110 families of probands with DCM and identified 102 individuals (24%) with suspected "early disease" (EDCM). Thirty-two EDCM subjects were randomised into a six-month placebo-controlled trial of the β-blocker, carvedilol. Transthoracic echocardiography and plasma nt-proBNP levels were measured at baseline and repeated at six months. The primary trial endpoint was change in left ventricular end-systolic diameter after six months. Subjects completing six months of blinded trial therapy were offered open-label carvedilol and then observed over an extended period with repeated clinical evaluation and echocardiography.
  
  
  RESULTS
  At baseline, left ventricular dimensions, systolic function and plasma nt-proBNP levels were similar in carvedilol and placebo groups. There were no significant changes observed in these parameters in either treatment group after six months, however reductions in end-diastolic diameter (% predicted) were observed in carvedilol-treated subjects (P=0.002) during an open-label median follow-up of 32 months (range: 13-56 months).
  
  
  CONCLUSIONS
  In an asymptomatic population of individuals with EDCM, treatment with carvedilol for six months had no effect on echocardiographic left ventricular dimensions or systolic function, however longer-term treatment may reverse left ventricular remodelling (Australian Clinical Trials Registry N012605000204640).
authors.affiliation: Molecular Cardiology Division, Victor Chang Cardiac Research Institute, Sydney, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Yeoh
authors.forename: Christopher
authors.initials: C
authors.lastname: Hayward
authors.forename: Victoria
authors.initials: V
authors.lastname: Benson
authors.forename: Angela
authors.initials: A
authors.lastname: Sheu
authors.forename: Zara
authors.initials: Z
authors.lastname: Richmond
authors.forename: Michael P
authors.initials: MP
authors.lastname: Feneley
authors.forename: Anne M
authors.initials: AM
authors.lastname: Keogh
authors.forename: Peter
authors.initials: P
authors.lastname: Macdonald
authors.forename: Diane
authors.initials: D
authors.lastname: Fatkin
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D002227:Carbazoles / Q000008:administration & dosage* / Q000009:adverse effects; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000077261:Carvedilol; D004452:Echocardiography; D005260:Female; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D011412:Propanolamines / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol