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


CONCLUSIONS
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.
Lacro
Ronald V
RV
Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA. ron.lacro@cardio.chboston.org
Dietz
Harry C
HC
Wruck
Lisa M
LM
Bradley
Timothy J
TJ
Colan
Steven D
SD
Devereux
Richard B
RB
Klein
Gloria L
GL
Li
Jennifer S
JS
Minich
L LuAnn
LL
Paridon
Stephen M
SM
Pearson
Gail D
GD
Printz
Beth F
BF
Pyeritz
Reed E
RE
Radojewski
Elizabeth
E
Roman
Mary J
MJ
Saul
J Philip
JP
Stylianou
Mario P
MP
Mahony
Lynn
L
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use*; D006801:Humans; D019808:Losartan / Q000627:therapeutic use*; D008382:Marfan Syndrome / Q000150:complications / Q000188:drug therapy*; D017063:Outcome Assessment, Health Care; D012107:Research Design
D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D001262:Atenolol; D019808:Losartan