Ronald V Lacro1, Harry C Dietz, Lynn A Sleeper, Anji T Yetman, Timothy J Bradley, Steven D Colan, Gail D Pearson, E Seda Selamet Tierney, Jami C Levine, Andrew M Atz, D Woodrow Benson, Alan C Braverman, Shan Chen, Julie De Backer, Bruce D Gelb, Paul D Grossfeld, Gloria L Klein, Wyman W Lai, Aimee Liou, Bart L Loeys, Larry W Markham, Aaron K Olson, Stephen M Paridon, Victoria L Pemberton, Mary Ella Pierpont, Reed E Pyeritz, Elizabeth Radojewski, Mary J Roman, Angela M Sharkey, Mario P Stylianou, Stephanie Burns Wechsler, Luciana T Young, Lynn Mahony. 1. 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.).
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.).
RCT Entities:
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.).
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