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

Lacro, R. V.; Dietz, H. C.; Sleeper, L. A.; Yetman, A. T.; Bradley, T. J.; Colan, S. D.; Pearson, G. D.; Selamet Tierney, E. S.; Levine, J. C.; Atz, A. M.; Benson, D. W.; Braverman, A. C.; Chen, S.; De Backer, J.; Gelb, B. D.; Grossfeld, P. D.; Klein, G. L.; Lai, W. W.; Liou, A.; Loeys, B. L.; Markham, L. W.; Olson, A. K.; Paridon, S. M.; Pemberton, V. L.; Pierpont, M. E.; Pyeritz, R. E.; Radojewski, E.; Roman, M. J.; Sharkey, A. M.; Stylianou, M. P.; Wechsler, S. B.; Young, L. T.; Mahony, L.

N Engl J Med. 2014 Nov 19; 371(22):2061-71

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.).

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