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Atenolol versus Losartan in Children and Young Adults with Marfan’s Syndrome

The New England journal of medicine | 19 Nov 2014

RV Lacro, HC Dietz, LA Sleeper, AT Yetman, TJ Bradley, SD Colan, GD Pearson, ES Tierney, JC Levine, AM Atz, DW Benson, AC Braverman, S Chen, J De Backer, BD Gelb, PD Grossfeld, GL Klein, WW Lai, A Liou, BL Loeys, LW Markham, AK Olson, SM Paridon, VL Pemberton, ME Pierpont, RE Pyeritz, E Radojewski, MJ Roman, AM Sharkey, MP Stylianou, SB Wechsler, LT Young and L Mahony
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 (±SE) in the 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 degree of aortic-root dilatation 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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Concepts
Cardiology, Pneumothorax, Losartan, Clinical trial, Beta blocker, Aorta, Aortic dissection, Marfan syndrome
MeSH headings
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