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

, ; Lacro, Ronald V; Dietz, Harry C; Sleeper, Lynn A; Yetman, Anji T; Bradley, Timothy J; Colan, Steven D; Pearson, Gail D; Selamet Tierney, E Seda and Levine, Jami C, et al. (2014) In New England Journal of Medicine 371(22). p.71-2061
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... (More)

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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Adrenergic beta-Antagonists/adverse effects, Adult, Angiotensin II Type 1 Receptor Blockers/adverse effects, Aorta/drug effects, Aortic Aneurysm/prevention & control, Aortic Valve Insufficiency, Atenolol/adverse effects, Child, Child, Preschool, Disease-Free Survival, Female, Humans, Infant, Linear Models, Losartan/adverse effects, Male, Marfan Syndrome/drug therapy, Treatment Outcome, Young Adult
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New England Journal of Medicine
volume
371
issue
22
pages
11 pages
publisher
Massachusetts Medical Society
external identifiers
  • scopus:84915756479
ISSN
0028-4793
DOI
10.1056/NEJMoa1404731
language
English
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3363b846-8ad8-4ef7-9c4b-a87d4f2c757b
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2019-01-25 14:44:19
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2019-10-20 05:13:46
@article{3363b846-8ad8-4ef7-9c4b-a87d4f2c757b,
  abstract     = {<p>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.</p><p>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.</p><p>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.</p><p>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.).</p>},
  author       = {,  and Lacro, Ronald V and Dietz, Harry C and Sleeper, Lynn A and Yetman, Anji T and Bradley, Timothy J and Colan, Steven D and Pearson, Gail D and Selamet Tierney, E Seda and Levine, Jami C and Atz, Andrew M and Benson, D Woodrow and Braverman, Alan C and Chen, Shan and De Backer, Julie and Gelb, Bruce D and Grossfeld, Paul D and Klein, Gloria L and Lai, Wyman W and Liou, Aimee and Loeys, Bart L and Markham, Larry W and Olson, Aaron K and Paridon, Stephen M and Pemberton, Victoria L and Pierpont, Mary Ella and Pyeritz, Reed E and Radojewski, Elizabeth and Roman, Mary J and Sharkey, Angela M and Stylianou, Mario P and Wechsler, Stephanie Burns and Young, Luciana T and Mahony, Lynn},
  issn         = {0028-4793},
  keyword      = {Adrenergic beta-Antagonists/adverse effects,Adult,Angiotensin II Type 1 Receptor Blockers/adverse effects,Aorta/drug effects,Aortic Aneurysm/prevention & control,Aortic Valve Insufficiency,Atenolol/adverse effects,Child,Child, Preschool,Disease-Free Survival,Female,Humans,Infant,Linear Models,Losartan/adverse effects,Male,Marfan Syndrome/drug therapy,Treatment Outcome,Young Adult},
  language     = {eng},
  month        = {11},
  number       = {22},
  pages        = {71--2061},
  publisher    = {Massachusetts Medical Society},
  series       = {New England Journal of Medicine},
  title        = {Atenolol versus losartan in children and young adults with Marfan's syndrome},
  url          = {http://dx.doi.org/10.1056/NEJMoa1404731},
  volume       = {371},
  year         = {2014},
}