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

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

Collaborators (158)

Pearson G, Stylianou M, Pemberton V, Mahony L, Sleeper L, Tennstedt S, Colan S, Klein G, Guey L, Wruck L, Travison T, Chen S, Gerstenberger E, Olesker T, Teitel DF, Newburger J, Lacro RV, King M, Dunbar-Masterson C, Handisides J, Posa A, Nang Q, Hass C, Hsu D, Lai W, Hellenbrand W, Printz B, Roman M, Devereux R, Korsin R, Sherwood G, Vetter V, Paridon S, Gleason M, Pyeritz R, Mirarchi N, DiLullo S, Ejembi A, Morgan R, Morrison T, Benson D, Border W, Cnota J, Heydarian H, Hamstra M, Hogan K, Bogenschutz L, Anderson PA, Li JS, Wechsler SB, Cook A, Sang C, Covitz W, Xu M, Sutton LJ, Crawford K, Roberts S, Palmer D, Saul J, Atz A, Forbus G, Atz T, Infinger P, Choudhury A, Minich L, Williams R, Yetman A, Shearrow M, Robinson M, Porter J, McCrindle B, Bradley T, Russell J, Colman J, Radojewski E, Khaikin S, Slater N, Dietz HC, Ravekes WJ, Rykiel M, Sparks E, Oswald G, Leadroot J, Canter C, Sharkey A, Braverman A, Rainey C, Jefferies JL, Slesnick T, Liou A, Martinez H, Menesses A, Tenende T, Liang D, Merkel E, Loeys B, De Backer J, Cobben JM, Sluysmans T, De Paepe A, De Nobele S, Gelb B, Srivastava S, Mendiz-Ramdeen T, Weismann C, Lawrence E, Chin S, Ko H, Yau JL, Webber S, Drant S, Luce J, Stiegler K, Markham L, Kinnard C, Stewart C, Sommers S, Madison C, Young L, Domenico M, Waitzman K, Lozano C, Pierpont ME, Baker C, Zielinski E, Vander Velden H, Overman A, Lewin M, Olson A, Payne A, Rimoin D, Pariani M, Siegel R, Rafique A, Grossfeld P, Smith A, McLees-Palinkas T, Colan SD, Selamet Tierney ES, Levine J, Trevey S, Rivera M, Artman M, Austin E, Baldwin H, Bernstein D, Feltes T, Johnson J, Klitzner T, Krischer J, Matherne G, Zahka KG, Kugler J, Driscoll DJ, Galantowicz M, Hunsberger SA, Knight TJ, Taylor H.

Author information

1
From Boston Children's Hospital, Boston (R.V.L., S.D.C., E.S.S.T., J.C.L.); Johns Hopkins University School of Medicine, Baltimore (H.C.D.); New England Research Institutes, Watertown, MA (L.A.S., S.D.C., S.C., G.L.K.); Primary Children's Hospital and the University of Utah, Salt Lake City (A.T.Y.); Hospital for Sick Children, Toronto (T.J.B., E.R.); National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (G.D.P., V.L.P., M.P.S.); Medical University of South Carolina, Charleston (A.M.A.); Cincinnati Children's Medical Center, Cincinnati (D.W.B.); Washington University School of Medicine, St. Louis (A.C.B., A.M.S.); Ghent University Hospital, Ghent, Belgium (J.D.B., B.L.L.); Icahn School of Medicine at Mount Sinai (B.D.G.), Children's Hospital of New York (W.W.L.), and Weill Medical College of Cornell University (M.J.R.) - all in New York; Rady Children's Hospital, University of California, San Diego (P.D.G.); Texas Children's Hospital, Houston (A.L.); Vanderbilt University School of Medicine, Nashville (L.W.M.); Seattle Children's Hospital, Seattle (A.K.O.); Children's Hospital of Philadelphia (S.M.P.) and the University of Pennsylvania (R.E.P.), Philadelphia; Children's Hospital and Clinics of Minnesota, Minneapolis (M.E.P.); Duke University Medical Center, Durham, NC (S.B.W.); Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago (L.T.Y.); and the University of Texas Southwestern Medical Center, Dallas (L.M.).

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.).

PMID:
25405392
PMCID:
PMC4386623
DOI:
10.1056/NEJMoa1404731
[Indexed for MEDLINE]
Free PMC Article

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