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

Ronald V. Lacro, Harry C Dietz, Lisa M. Wruck, Timothy J. Bradley, Steven D. Colan, Richard B. Devereux, Gloria L. Klein, Jennifer S. Li, L. LuAnn Minich, Stephen M. Paridon, Gail D. Pearson, Beth F. Printz, Reed E. Pyeritz, Elizabeth Radojewski, Mary J. Roman, J. Philip Saul, Mario P. Stylianou, Lynn Mahony

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)624-631
Number of pages8
JournalAmerican Heart Journal
Volume154
Issue number4
DOIs
StatePublished - Oct 2007

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Marfan Syndrome
Atenolol
Losartan
Angiotensin Receptor Antagonists
Randomized Controlled Trials
Growth
Dissection
Sinus of Valsalva
Aortic Diseases
Vascular Stiffness
Aortic Valve Insufficiency
Mortality
Body Surface Area
Incidence
Mitral Valve Insufficiency
Therapeutics
Life Expectancy
Drug-Related Side Effects and Adverse Reactions
Left Ventricular Function
Rupture

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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. / 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.

In: American Heart Journal, Vol. 154, No. 4, 10.2007, p. 624-631.

Research output: Contribution to journalArticle

Lacro, RV, Dietz, HC, Wruck, LM, Bradley, TJ, Colan, SD, Devereux, RB, Klein, GL, Li, JS, Minich, LL, Paridon, SM, Pearson, GD, Printz, BF, Pyeritz, RE, Radojewski, E, Roman, MJ, Saul, JP, Stylianou, MP & Mahony, L 2007, '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', American Heart Journal, vol. 154, no. 4, pp. 624-631. https://doi.org/10.1016/j.ahj.2007.06.024
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. / 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. In: American Heart Journal. 2007 ; Vol. 154, No. 4. pp. 624-631.
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abstract = "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.",
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AU - Wruck, Lisa M.

AU - Bradley, Timothy J.

AU - Colan, Steven D.

AU - Devereux, Richard B.

AU - Klein, Gloria L.

AU - Li, Jennifer S.

AU - Minich, L. LuAnn

AU - Paridon, Stephen M.

AU - Pearson, Gail D.

AU - Printz, Beth F.

AU - Pyeritz, Reed E.

AU - Radojewski, Elizabeth

AU - Roman, Mary J.

AU - Saul, J. Philip

AU - Stylianou, Mario P.

AU - Mahony, Lynn

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