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 in: The American heart journal Vol. 154; no. 4; pp. 624 - 631
• Main Authors: Lacro, Ronald V., Dietz, Harry C., Wruck, Lisa M., Bradley, Timothy J., Colan, Steven D., Devereux, Richard B., Klein, Gloria L., Li, Jennifer S., Minich, L. LuAnn, Paridon, Stephen M., Pearson, Gail D., Printz, Beth F., Pyeritz, Reed E., Radojewski, Elizabeth, Roman, Mary J., Saul, J. Philip, Stylianou, Mario P., Mahony, Lynn
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.10.2007; Elsevier
• Subjects: Adrenergic beta-Antagonists - therapeutic use; Adult; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Atenolol - therapeutic use; Biological and medical sciences; Cardiology. Vascular system; Cardiovascular; Humans; Losartan - therapeutic use; Marfan Syndrome - complications; Marfan Syndrome - drug therapy; Medical sciences; Outcome Assessment, Health Care; Research Design; Human; Connective tissue disease; Therapy; Skin disease; Elastic tissue disease; Atenolol; Phlebology; Marfan syndrome; Genetic disease; Design; Goal; Randomization; Treatment; Individual; Losartan; Systemic disease; Clinical trial; Angiotensin antagonist; Circulatory system; Cardiology; Comparative study
• ISSN: 0002-8703; 1097-6744; 1097-6744
• DOI: 10.1016/j.ahj.2007.06.024

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. 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. 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.