Rationale and design of a randomized clinical trial of β-blocker therapy (atenolol) versus angiotensin II receptor blocker therapy (losartan) in individuals with Marfan syndrome

Published on Oct 1, 2007in American Heart Journal4.02
· DOI :10.1016/j.ahj.2007.06.024
Ronald V. Lacro28
Estimated H-index: 28
(Harvard University),
Harry C. Dietz86
Estimated H-index: 86
(Johns Hopkins University)
+ 15 AuthorsLynn Mahony30
Estimated H-index: 30
(UTSW: University of Texas Southwestern Medical Center)
Background Cardiovascular disease, including aortic root dilation, dissection, and rupture, is the leading cause of mortality in patients with Marfan syndrome (MFS). The maximal aortic root diameter at the sinuses of Valsalva is considered the best predictor of adverse cardiovascular outcome. Although advances in therapy have improved life expectancy, affected individuals continue to suffer cardiovascular morbidity and mortality. Recent studies in an FBN1 -targeted mouse model of MFS with aortic disease similar to that seen in humans showed that treatment with losartan normalized aortic root growth and aortic wall architecture. Methods The Pediatric Heart Network designed a randomized clinical trial to compare aortic root growth and other short-term cardiovascular outcomes in subjects with MFS receiving atenolol or losartan. Individuals 6 months to 25 years of age with a body surface area–adjusted aortic root z score >3.0 will be eligible for inclusion. The primary aim is to compare the effect of atenolol therapy with that of losartan therapy on the rate of aortic root growth over 3 years. Secondary end points include progression of aortic regurgitation; incidence of aortic dissection, aortic root surgery, and death; progression of mitral regurgitation; left ventricular size and function; echocardiographically derived measures of central aortic stiffness; skeletal and somatic growth; and incidence of adverse drug reactions. Conclusion This randomized trial should make a substantial contribution to the management of individuals with MFS and expand our understanding of the mechanisms responsible for the aortic manifestations of this disorder.
  • References (34)
  • Citations (194)
#1Lynn Mahony (UTSW: University of Texas Southwestern Medical Center)H-Index: 30
#2Lynn A. SleeperH-Index: 69
Last.G. D. Pearson (UTSW: University of Texas Southwestern Medical Center)H-Index: 1
view all 10 authors...
#1Daniel P. Judge (Johns Hopkins University)H-Index: 39
#2Harry C. Dietz (Johns Hopkins University)H-Index: 86
#1Angela T Yetman (Anschutz Medical Campus)H-Index: 8
#2Renee A. Bornemeier (University of Arkansas for Medical Sciences)H-Index: 9
Last.Brian W. McCrindle (U of T: University of Toronto)H-Index: 86
view all 3 authors...
#1Bart Loeys (Johns Hopkins University)H-Index: 56
#2Junji Chen (Johns Hopkins University)H-Index: 1
Last.Neda Sharifi (Johns Hopkins University)H-Index: 2
view all 10 authors...
#2Nan M. LairdH-Index: 97
Last.James H. Ware (Harvard University)H-Index: 73
view all 3 authors...
Cited By194
#1Fabian Emrich (Stanford University)H-Index: 8
#2Kiril Penov (Stanford University)H-Index: 5
Last.Andrew J. Connolly (Stanford University)H-Index: 39
view all 10 authors...
#1Marion A. Hofmann Bowman (UM: University of Michigan)H-Index: 1
#2Kim A. Eagle (UM: University of Michigan)H-Index: 115
Last.Dianna M. Milewicz (University of Texas Health Science Center at Houston)H-Index: 56
view all 3 authors...
#1Alan C. Braverman (WashU: Washington University in St. Louis)H-Index: 23
#1Arvind Hoskoppal (UofU: University of Utah)H-Index: 1
#2Shaji C. Menon (UofU: University of Utah)H-Index: 17
Last.Wyman W. Lai (Columbia University)H-Index: 9
view all 10 authors...
#1Douglas Y. Mah (Boston Children's Hospital)H-Index: 14
#2Lynn A. Sleeper (Boston Children's Hospital)H-Index: 69
Last.Elif Seda Selamet Tierney (Boston Children's Hospital)H-Index: 17
view all 10 authors...
#1Elif Seda Selamet Tierney (Boston Children's Hospital)H-Index: 17
#2Jami C. Levine (Boston Children's Hospital)H-Index: 22
Last.De Backer J (Ghent University Hospital)H-Index: 39
view all 10 authors...
#1John Dean (ARI: Aberdeen Royal Infirmary)H-Index: 11
#2Bart LoeysH-Index: 56
View next paperEffect of perindopril on large artery stiffness and aortic root diameter in patients with Marfan syndrome: a randomized controlled trial.