Atenolol versus losartan in children and young adults with Marfan's syndrome
Ronald V Lacro, Harry C Dietz, Lynn A Sleeper, Anji 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, 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, Pediatric Heart Network Investigators, Gail Pearson, Mario Stylianou, Victoria Pemberton, Lynn Mahony, Lynn Sleeper, Sharon Tennstedt, Steven Colan, Gloria Klein, Lin Guey, Lisa Wruck, Thomas Travison, Shan Chen, Eric Gerstenberger, Tanya Olesker, David F Teitel, Jane Newburger, Ronald V Lacro, Martha King, Carolyn Dunbar-Masterson, Jill Handisides, Andrea Posa, Quincy Nang, Cara Hass, Daphne Hsu, Wyman Lai, William Hellenbrand, Beth Printz, Mary Roman, Richard Devereux, Rosalind Korsin, Greysi Sherwood, Victoria Vetter, Stephen Paridon, Marie Gleason, Reed Pyeritz, Nicole Mirarchi, Sandra DiLullo, Agbenu Ejembi, Ruth Morgan, Tonia Morrison, D Woodrow Benson, William Border, James Cnota, Haleh Heydarian, Michelle Hamstra, Kathryn Hogan, Lois Bogenschutz, Page A W Anderson, Jennifer S Li, Stephanie Burns Wechsler, Amanda Cook, Charles Sang, Wesley Covitz, Mingfen Xu, Lori Jo Sutton, Kari Crawford, Summer Roberts, Deborah Palmer, J Philip Saul, Andrew Atz, Geoffrey Forbus, Teresa Atz, Patricia Infinger, Aparna Choudhury, LuAnn Minich, Richard Williams, Angela Yetman, Marian Shearrow, Michelle Robinson, June Porter, Brian McCrindle, Timothy Bradley, Jennifer Russell, Jack Colman, Elizabeth Radojewski, Svetlana Khaikin, Nancy Slater, Harry C Dietz, William J Ravekes, Mary Rykiel, Elisabeth Sparks, Gretchen Oswald, Jennifer Leadroot, Charles Canter, Angela Sharkey, Alan Braverman, Cheryl Rainey, John L Jefferies, Timothy Slesnick, Aimee Liou, Hugo Martinez, Andres Menesses, Tunu Tenende, David Liang, Elisabeth Merkel, Bart Loeys, Julie De Backer, Jan Maarten Cobben, Thierry Sluysmans, Anne De Paepe, Sylvia De Nobele, Bruce Gelb, Shubhika Srivastava, Tejani Mendiz-Ramdeen, Constance Weismann, Emily Lawrence, Stephanie Chin, Helen Ko, Jen Le Yau, Steven Webber, Stacey Drant, Jane Luce, Kevin Stiegler, Larry Markham, Cheryl Kinnard, Cheri Stewart, Sue Sommers, Carol Madison, Luciana Young, Megan Domenico, Kathryn Waitzman, Carla Lozano, Mary Ella Pierpont, Charles Baker, Erin Zielinski, Heidi Vander Velden, Alison Overman, Mark Lewin, Aaron Olson, Amy Payne, David Rimoin, Mitchel Pariani, Robert Siegel, Asim Rafique, Paul Grossfeld, Arlene Smith, Terri McLees-Palinkas, Steven D Colan, Elif Seda Selamet Tierney, Jami Levine, Shari Trevey, Marga Rivera, Michael Artman, Erle Austin, H Scott Baldwin, Daniel Bernstein, Timothy Feltes, Julie Johnson, Thomas Klitzner, Jeffrey Krischer, G Paul Matherne, Kenneth G Zahka, John Kugler, David J Driscoll, Mark Galantowicz, Sally A Hunsberger, Thomas J Knight, Holly Taylor, Ronald V Lacro, Harry C Dietz, Lynn A Sleeper, Anji 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, 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, Pediatric Heart Network Investigators, Gail Pearson, Mario Stylianou, Victoria Pemberton, Lynn Mahony, Lynn Sleeper, Sharon Tennstedt, Steven Colan, Gloria Klein, Lin Guey, Lisa Wruck, Thomas Travison, Shan Chen, Eric Gerstenberger, Tanya Olesker, David F Teitel, Jane Newburger, Ronald V Lacro, Martha King, Carolyn Dunbar-Masterson, Jill Handisides, Andrea Posa, Quincy Nang, Cara Hass, Daphne Hsu, Wyman Lai, William Hellenbrand, Beth Printz, Mary Roman, Richard Devereux, Rosalind Korsin, Greysi Sherwood, Victoria Vetter, Stephen Paridon, Marie Gleason, Reed Pyeritz, Nicole Mirarchi, Sandra DiLullo, Agbenu Ejembi, Ruth Morgan, Tonia Morrison, D Woodrow Benson, William Border, James Cnota, Haleh Heydarian, Michelle Hamstra, Kathryn Hogan, Lois Bogenschutz, Page A W Anderson, Jennifer S Li, Stephanie Burns Wechsler, Amanda Cook, Charles Sang, Wesley Covitz, Mingfen Xu, Lori Jo Sutton, Kari Crawford, Summer Roberts, Deborah Palmer, J Philip Saul, Andrew Atz, Geoffrey Forbus, Teresa Atz, Patricia Infinger, Aparna Choudhury, LuAnn Minich, Richard Williams, Angela Yetman, Marian Shearrow, Michelle Robinson, June Porter, Brian McCrindle, Timothy Bradley, Jennifer Russell, Jack Colman, Elizabeth Radojewski, Svetlana Khaikin, Nancy Slater, Harry C Dietz, William J Ravekes, Mary Rykiel, Elisabeth Sparks, Gretchen Oswald, Jennifer Leadroot, Charles Canter, Angela Sharkey, Alan Braverman, Cheryl Rainey, John L Jefferies, Timothy Slesnick, Aimee Liou, Hugo Martinez, Andres Menesses, Tunu Tenende, David Liang, Elisabeth Merkel, Bart Loeys, Julie De Backer, Jan Maarten Cobben, Thierry Sluysmans, Anne De Paepe, Sylvia De Nobele, Bruce Gelb, Shubhika Srivastava, Tejani Mendiz-Ramdeen, Constance Weismann, Emily Lawrence, Stephanie Chin, Helen Ko, Jen Le Yau, Steven Webber, Stacey Drant, Jane Luce, Kevin Stiegler, Larry Markham, Cheryl Kinnard, Cheri Stewart, Sue Sommers, Carol Madison, Luciana Young, Megan Domenico, Kathryn Waitzman, Carla Lozano, Mary Ella Pierpont, Charles Baker, Erin Zielinski, Heidi Vander Velden, Alison Overman, Mark Lewin, Aaron Olson, Amy Payne, David Rimoin, Mitchel Pariani, Robert Siegel, Asim Rafique, Paul Grossfeld, Arlene Smith, Terri McLees-Palinkas, Steven D Colan, Elif Seda Selamet Tierney, Jami Levine, Shari Trevey, Marga Rivera, Michael Artman, Erle Austin, H Scott Baldwin, Daniel Bernstein, Timothy Feltes, Julie Johnson, Thomas Klitzner, Jeffrey Krischer, G Paul Matherne, Kenneth G Zahka, John Kugler, David J Driscoll, Mark Galantowicz, Sally A Hunsberger, Thomas J Knight, Holly Taylor
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.).
Figures
Source: PubMed