Atenolol versus losartan in children and young adults with Marfan's syndrome. N Engl J Med 2014 Nov 27;371(22):2061-71
Date
11/19/2014Pubmed ID
25405392Pubmed Central ID
PMC4386623DOI
10.1056/NEJMoa1404731Scopus ID
2-s2.0-84915756479 (requires institutional sign-in at Scopus site) 446 CitationsAbstract
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.).
Author List
Lacro RV, Dietz HC, Sleeper LA, Yetman AT, Bradley TJ, Colan SD, Pearson GD, Selamet Tierney ES, Levine JC, Atz AM, Benson DW, Braverman AC, Chen S, De Backer J, Gelb BD, Grossfeld PD, Klein GL, Lai WW, Liou A, Loeys BL, Markham LW, Olson AK, Paridon SM, Pemberton VL, Pierpont ME, Pyeritz RE, Radojewski E, Roman MJ, Sharkey AM, Stylianou MP, Wechsler SB, Young LT, Mahony L, Pediatric Heart Network InvestigatorsMESH terms used to index this publication - Major topics in bold
Adrenergic beta-AntagonistsAdult
Angiotensin II Type 1 Receptor Blockers
Aorta
Aortic Aneurysm
Aortic Valve Insufficiency
Atenolol
Child
Child, Preschool
Disease-Free Survival
Female
Humans
Infant
Linear Models
Losartan
Male
Marfan Syndrome
Treatment Outcome
Young Adult
