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

Ronald V. Lacro, Harry C. Dietz, Lynn A. Sleeper, Angela T Yetman, Timothy J. Bradley, Steven D. Colan, Gail D. Pearson, E. Seda Selamet Tierney, Jami C. Levine, Andrew M. Atz, D. Woodrow Benson, Alan C. Braverman, Shan Chen, Julie De Backer, Bruce D. Gelb, Paul D. Grossfeld, Gloria L. Klein, Wyman W. Lai, Aimee Liou, Bart L. Loeys & 13 others Larry W. Markham, Aaron K. Olson, Stephen M. Paridon, Victoria L. Pemberton, Mary Ella Pierpont, Reed E. Pyeritz, Elizabeth Radojewski, Mary J. Roman, Angela M. Sharkey, Mario P. Stylianou, Stephanie Burns Wechsler, Luciana T. Young, Lynn Mahony

Research output: Contribution to journalArticle

222 Citations (Scopus)

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 aorticroot 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 aorticroot z score greater than 3.0. The baseline-adjusted rate of change (±SE) in the 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 degree of aortic-root dilatation 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 aorticroot 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.)

Original languageEnglish (US)
Pages (from-to)2061-2071
Number of pages11
JournalNew England Journal of Medicine
Volume371
Issue number22
DOIs
StatePublished - Nov 27 2014

Fingerprint

Marfan Syndrome
Atenolol
Losartan
Young Adult
Dissection
Body Surface Area
Dilatation
National Heart, Lung, and Blood Institute (U.S.)
Aortic Valve Insufficiency
Therapeutics
Cause of Death
Incidence
Growth

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lacro, R. V., Dietz, H. C., Sleeper, L. A., Yetman, A. T., Bradley, T. J., Colan, S. D., ... Mahony, L. (2014). Atenolol versus losartan in children and young adults with Marfan's syndrome. New England Journal of Medicine, 371(22), 2061-2071. https://doi.org/10.1056/NEJMoa1404731

Atenolol versus losartan in children and young adults with Marfan's syndrome. / Lacro, Ronald V.; Dietz, Harry C.; Sleeper, Lynn A.; Yetman, Angela T; Bradley, Timothy J.; Colan, Steven D.; Pearson, Gail D.; Selamet Tierney, E. Seda; Levine, Jami C.; Atz, Andrew M.; Benson, D. Woodrow; Braverman, Alan C.; Chen, Shan; De Backer, Julie; Gelb, Bruce D.; Grossfeld, Paul D.; Klein, Gloria L.; Lai, Wyman W.; Liou, Aimee; Loeys, Bart L.; Markham, Larry W.; Olson, Aaron K.; Paridon, Stephen M.; Pemberton, Victoria L.; Pierpont, Mary Ella; Pyeritz, Reed E.; Radojewski, Elizabeth; Roman, Mary J.; Sharkey, Angela M.; Stylianou, Mario P.; Wechsler, Stephanie Burns; Young, Luciana T.; Mahony, Lynn.

In: New England Journal of Medicine, Vol. 371, No. 22, 27.11.2014, p. 2061-2071.

Research output: Contribution to journalArticle

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 2014, 'Atenolol versus losartan in children and young adults with Marfan's syndrome', New England Journal of Medicine, vol. 371, no. 22, pp. 2061-2071. https://doi.org/10.1056/NEJMoa1404731
Lacro, Ronald V. ; Dietz, Harry C. ; Sleeper, Lynn A. ; Yetman, Angela T ; Bradley, Timothy J. ; Colan, Steven D. ; Pearson, Gail D. ; Selamet Tierney, E. Seda ; Levine, Jami C. ; Atz, Andrew M. ; Benson, D. Woodrow ; Braverman, Alan C. ; Chen, Shan ; De Backer, Julie ; Gelb, Bruce D. ; Grossfeld, Paul D. ; Klein, Gloria L. ; Lai, Wyman W. ; Liou, Aimee ; Loeys, Bart L. ; Markham, Larry W. ; Olson, Aaron K. ; Paridon, Stephen M. ; Pemberton, Victoria L. ; Pierpont, Mary Ella ; Pyeritz, Reed E. ; Radojewski, Elizabeth ; Roman, Mary J. ; Sharkey, Angela M. ; Stylianou, Mario P. ; Wechsler, Stephanie Burns ; Young, Luciana T. ; Mahony, Lynn. / Atenolol versus losartan in children and young adults with Marfan's syndrome. In: New England Journal of Medicine. 2014 ; Vol. 371, No. 22. pp. 2061-2071.
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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 aorticroot 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 aorticroot z score greater than 3.0. The baseline-adjusted rate of change (±SE) in the 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 degree of aortic-root dilatation 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 aorticroot 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 = "Lacro, {Ronald V.} and Dietz, {Harry C.} and Sleeper, {Lynn A.} and Yetman, {Angela 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 Shan Chen and {De Backer}, Julie and Gelb, {Bruce D.} and Grossfeld, {Paul D.} and Klein, {Gloria L.} and Lai, {Wyman W.} and Aimee Liou 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 Elizabeth Radojewski and Roman, {Mary J.} and Sharkey, {Angela M.} and Stylianou, {Mario P.} and Wechsler, {Stephanie Burns} and Young, {Luciana T.} and Lynn Mahony",
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T1 - Atenolol versus losartan in children and young adults with Marfan's syndrome

AU - Lacro, Ronald V.

AU - Dietz, Harry C.

AU - Sleeper, Lynn A.

AU - Yetman, Angela T

AU - Bradley, Timothy J.

AU - Colan, Steven D.

AU - Pearson, Gail D.

AU - Selamet Tierney, E. Seda

AU - Levine, Jami C.

AU - Atz, Andrew M.

AU - Benson, D. Woodrow

AU - Braverman, Alan C.

AU - Chen, Shan

AU - De Backer, Julie

AU - Gelb, Bruce D.

AU - Grossfeld, Paul D.

AU - Klein, Gloria L.

AU - Lai, Wyman W.

AU - Liou, Aimee

AU - Loeys, Bart L.

AU - Markham, Larry W.

AU - Olson, Aaron K.

AU - Paridon, Stephen M.

AU - Pemberton, Victoria L.

AU - Pierpont, Mary Ella

AU - Pyeritz, Reed E.

AU - Radojewski, Elizabeth

AU - Roman, Mary J.

AU - Sharkey, Angela M.

AU - Stylianou, Mario P.

AU - Wechsler, Stephanie Burns

AU - Young, Luciana T.

AU - Mahony, Lynn

PY - 2014/11/27

Y1 - 2014/11/27

N2 - 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 aorticroot 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 aorticroot z score greater than 3.0. The baseline-adjusted rate of change (±SE) in the 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 degree of aortic-root dilatation 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 aorticroot 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.)

AB - 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 aorticroot 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 aorticroot z score greater than 3.0. The baseline-adjusted rate of change (±SE) in the 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 degree of aortic-root dilatation 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 aorticroot 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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