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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 ; Levine, Jami C and Atz, Andrew M , 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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publication status
published
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keywords
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
in
New England Journal of Medicine
volume
371
issue
22
pages
11 pages
publisher
Massachusetts Medical Society
external identifiers
  • pmid:25405392
  • scopus:84915756479
ISSN
0028-4793
DOI
10.1056/NEJMoa1404731
language
English
LU publication?
no
id
3363b846-8ad8-4ef7-9c4b-a87d4f2c757b
date added to LUP
2019-01-25 14:44:19
date last changed
2023-01-23 03:26:31
@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       = {{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}},
  keywords     = {{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}},
  doi          = {{10.1056/NEJMoa1404731}},
  volume       = {{371}},
  year         = {{2014}},
}