American Heart Journal
Volume 154, Issue 4 , Pages 624-631, October 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

  • Ronald V. Lacro, MD

      Affiliations

    • Children's Hospital Boston and Harvard Medical School, Boston, MA
    • Corresponding Author InformationReprint requests: Ronald V. Lacro, MD, Department of Cardiology, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115.
    • ,
  • Harry C. Dietz, MD

      Affiliations

    • Johns Hopkins University, Baltimore, MD
    • ,
  • Lisa M. Wruck, PhD

      Affiliations

    • New England Research Institutes, Watertown, MA
    • ,
  • Timothy J. Bradley, MD

      Affiliations

    • The Hospital for Sick Children, Toronto, Ontario, Canada
    • ,
  • Steven D. Colan, MD

      Affiliations

    • Children's Hospital Boston and Harvard Medical School, Boston, MA
    • New England Research Institutes, Watertown, MA
    • ,
  • Richard B. Devereux, MD

      Affiliations

    • Weill Medical College of Cornell University, New York, NY
    • ,
  • Gloria L. Klein, MS

      Affiliations

    • New England Research Institutes, Watertown, MA
    • ,
  • Jennifer S. Li, MD

      Affiliations

    • Duke University Medical Center, Durham, NC
    • ,
  • L. LuAnn Minich, MD

      Affiliations

    • Primary Children's Medical Center, Salt Lake City, UT
    • ,
  • Stephen M. Paridon, MD

      Affiliations

    • The Children's Hospital of Philadelphia, Philadelphia, PA
    • ,
  • Gail D. Pearson, MD, ScD

      Affiliations

    • National Heart, Lung, and Blood Institute, Bethesda, MD
    • ,
  • Beth F. Printz, MD

      Affiliations

    • Columbia University Medical Center, New York, NY
    • ,
  • Reed E. Pyeritz, MD, PhD

      Affiliations

    • University of Pennsylvania, Philadelphia, PA
    • ,
  • Elizabeth Radojewski, RN

      Affiliations

    • The Hospital for Sick Children, Toronto, Ontario, Canada
    • ,
  • Mary J. Roman, MD

      Affiliations

    • Weill Medical College of Cornell University, New York, NY
    • ,
  • J. Philip Saul, MD

      Affiliations

    • Medical University of South Carolina, Charleston, SC
    • ,
  • Mario P. Stylianou, PhD

      Affiliations

    • National Heart, Lung, and Blood Institute, Bethesda, MD
    • ,
  • Lynn Mahony, MD,

      Affiliations

    • University of Texas Southwestern Medical Center, Dallas, TX
    • ,
  • for the Pediatric Heart Network Investigators

Received 5 February 2007; accepted 20 June 2007. published online 07 August 2007.

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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 This work was supported by U01 HL068285 (Lacro); U01 HL068270 (Wruck, Mahony, Colan, Klein), U01 HL068269 (Li), U01 HL068292 (Minich), U01 HL068290 (Printz, Devereux, Roman), U01 HL068288 (Bradley), U01 HL068281 (Saul), and U01 HL068279 (Paridon, Pyeritz) from the National Heart, Lung, and Blood Institute (Bethesda, MD), the Howard Hughes Medical Institute (Baltimore, MD) (Dietz); the National Marfan Foundation (Port Washington, NY) (Dietz); and the Smilow Center for Marfan Syndrome Research (Baltimore, MD) (Dietz).

PII: S0002-8703(07)00528-5

doi:10.1016/j.ahj.2007.06.024

American Heart Journal
Volume 154, Issue 4 , Pages 624-631, October 2007

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