Effects of Losartan Versus Atenolol on Aortic and Cardiac Muscle Stiffness in Adults With Marfan Syndrome
Marfan syndrome is an inherited connective tissue disorder with morbidity and mortality from aortic dilation and dissection. The degree of aortic dilation and response to beta-blockade (standard of care) vary in adults with Marfan syndrome. However, aortic stiffness is often present, and can be a predictor of aortic dilation and cardiovascular complications. In addition, adults with Marfan syndrome develop left ventricular diastolic dysfunction, which can progress to heart failure. Aortic stiffness and diastolic dysfunction are important and logical therapeutic targets in adults with Marfan syndrome.
TGF-beta mediates disease pathogenesis in Marfan syndrome and contributes to aortic stiffness. The angiotensin receptor blocker, losartan, inhibits TGF-beta activity and reverses aortic wall pathology in a Marfan mouse model. Losartan also decreases aortic stiffness and improves diastolic function in hypertension, renal disease and hypertrophic cardiomyopathy.
This trial is a randomized, double-blind trial of 50 adults with Marfan syndrome, treated with 6 months of atenolol vs. losartan. Arterial tonometry for aortic stiffness and echocardiography for diastolic function will be performed at the beginning and end of treatment. A blood draw for serum markers of extracellular matrix turnover and inflammation will also be performed at 0 and 6 months. We plan to determine whether losartan decreases aortic stiffness and left ventricular diastolic dysfunction significantly more than atenolol.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Effects of Losartan vs Atenolol on Aortic Stiffness and Diastolic Function in Adults With Marfan Syndrome|
- Aortic biophysical properties [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Diastolic Function [ Time Frame: 6 months ] [ Designated as safety issue: No ]
|Study Start Date:||October 2007|
|Study Completion Date:||December 2012|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Active Comparator: 1
Atenolol 50mg PO QD
Other Name: Tenormin
Losartan 100mg PO QD
Other Name: Cozaar
Please See Summary.
|United States, Massachusetts|
|Brigham and Women's Hospital|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||Mark A Creager, MD||Brigham and Women;s Hospital|