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

Research output: Contribution to journalArticle

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.).

Details

Authors
External organisations
  • Mount Sinai Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cardiac and Cardiovascular Systems
  • Pediatrics

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
Original languageEnglish
Pages (from-to)2061-71
Number of pages11
JournalNew England Journal of Medicine
Volume371
Issue number22
Publication statusPublished - 2014 Nov 27
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes