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Atenolol versus losartan in children and young adults with Marfan's syndrome.

The New England journal of medicine (2014-11-19)
Ronald V Lacro, 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
ABSTRACT

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. 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. 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. 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.).

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Atenolol, ≥98% (TLC), powder
USP
Atenolol, United States Pharmacopeia (USP) Reference Standard
Atenolol, European Pharmacopoeia (EP) Reference Standard