title: Atenolol versus losartan in children and young adults with Marfan's syndrome.
abstract: BACKGROUND
  Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers.
  
  
  METHODS
  We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events.
  
  
  RESULTS
  From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean [±SD] age, 11.5±6.5 years in the atenolol group and 11.0±6.2 years in the losartan group), who had an aortic-root z score greater than 3.0. The baseline-adjusted rate of change in the mean (±SE) aortic-root z score did not differ significantly between the atenolol group and the losartan group (-0.139±0.013 and -0.107±0.013 standard-deviation units per year, respectively; P=0.08). Both slopes were significantly less than zero, indicating a decrease in the aortic-root diameter relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups.
  
  
  CONCLUSIONS
  Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aortic-root dilatation between the two treatment groups over a 3-year period. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00429364.).
authors.affiliation: From Boston Children's Hospital, Boston (R.V.L., S.D.C., E.S.S.T., J.C.L.); Johns Hopkins University School of Medicine, Baltimore (H.C.D.); New England Research Institutes, Watertown, MA (L.A.S., S.D.C., S.C., G.L.K.); Primary Children's Hospital and the University of Utah, Salt Lake City (A.T.Y.); Hospital for Sick Children, Toronto (T.J.B., E.R.); National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (G.D.P., V.L.P., M.P.S.); Medical University of South Carolina, Charleston (A.M.A.); Cincinnati Children's Medical Center, Cincinnati (D.W.B.); Washington University School of Medicine, St. Louis (A.C.B., A.M.S.); Ghent University Hospital, Ghent, Belgium (J.D.B., B.L.L.); Icahn School of Medicine at Mount Sinai (B.D.G.), Children's Hospital of New York (W.W.L.), and Weill Medical College of Cornell University (M.J.R.) - all in New York; Rady Children's Hospital, University of California, San Diego (P.D.G.); Texas Children's Hospital, Houston (A.L.); Vanderbilt University School of Medicine, Nashville (L.W.M.); Seattle Children's Hospital, Seattle (A.K.O.); Children's Hospital of Philadelphia (S.M.P.) and the University of Pennsylvania (R.E.P.), Philadelphia; Children's Hospital and Clinics of Minnesota, Minneapolis (M.E.P.); Duke University Medical Center, Durham, NC (S.B.W.); Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago (L.T.Y.); and the University of Texas Southwestern Medical Center, Dallas (L.M.).
authors.forename: Ronald V
authors.initials: RV
authors.lastname: Lacro
authors.forename: Harry C
authors.initials: HC
authors.lastname: Dietz
authors.forename: Lynn A
authors.initials: LA
authors.lastname: Sleeper
authors.forename: Anji T
authors.initials: AT
authors.lastname: Yetman
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Bradley
authors.forename: Steven D
authors.initials: SD
authors.lastname: Colan
authors.forename: Gail D
authors.initials: GD
authors.lastname: Pearson
authors.forename: E Seda
authors.initials: ES
authors.lastname: Selamet Tierney
authors.forename: Jami C
authors.initials: JC
authors.lastname: Levine
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Atz
authors.forename: D Woodrow
authors.initials: DW
authors.lastname: Benson
authors.forename: Alan C
authors.initials: AC
authors.lastname: Braverman
authors.forename: Shan
authors.initials: S
authors.lastname: Chen
authors.forename: Julie
authors.initials: J
authors.lastname: De Backer
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Gelb
authors.forename: Paul D
authors.initials: PD
authors.lastname: Grossfeld
authors.forename: Gloria L
authors.initials: GL
authors.lastname: Klein
authors.forename: Wyman W
authors.initials: WW
authors.lastname: Lai
authors.forename: Aimee
authors.initials: A
authors.lastname: Liou
authors.forename: Bart L
authors.initials: BL
authors.lastname: Loeys
authors.forename: Larry W
authors.initials: LW
authors.lastname: Markham
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Olson
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Paridon
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Pemberton
authors.forename: Mary Ella
authors.initials: ME
authors.lastname: Pierpont
authors.forename: Reed E
authors.initials: RE
authors.lastname: Pyeritz
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Radojewski
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Roman
authors.forename: Angela M
authors.initials: AM
authors.lastname: Sharkey
authors.forename: Mario P
authors.initials: MP
authors.lastname: Stylianou
authors.forename: Stephanie Burns
authors.initials: SB
authors.lastname: Wechsler
authors.forename: Luciana T
authors.initials: LT
authors.lastname: Young
authors.forename: Lynn
authors.initials: L
authors.lastname: Mahony
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D001011:Aorta / Q000187:drug effects* / Q000254:growth & development / Q000601:surgery; D001014:Aortic Aneurysm / Q000517:prevention & control*; D001022:Aortic Valve Insufficiency; D001262:Atenolol / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D016014:Linear Models; D019808:Losartan / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008382:Marfan Syndrome / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D001262:Atenolol; D019808:Losartan