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

N Engl J Med. 2014 Nov 27;371(22):2061-71. doi: 10.1056/NEJMoa1404731. Epub 2014 Nov 18.

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.).

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic beta-Antagonists / adverse effects
  • Adrenergic beta-Antagonists / therapeutic use*
  • Adult
  • Angiotensin II Type 1 Receptor Blockers / adverse effects
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Aorta / drug effects*
  • Aorta / growth & development
  • Aorta / surgery
  • Aortic Aneurysm / prevention & control*
  • Aortic Valve Insufficiency
  • Atenolol / adverse effects
  • Atenolol / therapeutic use*
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Humans
  • Infant
  • Linear Models
  • Losartan / adverse effects
  • Losartan / therapeutic use*
  • Male
  • Marfan Syndrome / drug therapy*
  • Marfan Syndrome / mortality
  • Marfan Syndrome / physiopathology
  • Treatment Outcome
  • Young Adult

Substances

  • Adrenergic beta-Antagonists
  • Angiotensin II Type 1 Receptor Blockers
  • Atenolol
  • Losartan

Associated data

  • ClinicalTrials.gov/NCT00429364