Abstract
Objective
To assess the tolerability and efficacy of the investigational use of the angiotensin
II receptor blocker losartan added to β-blockade (BB) to prevent progressive aortic
root dilation in patients with Marfan syndrome (MFS).
Patients and Methods
Between May 1, 2007, and September 31, 2011, 28 patients with MFS (11 males [39%];
mean ± SD age, 13.1±6.3 years) with recognized aortic root dilation (z score >2.0) and receiving BB (atenolol or propranolol) treatment were enrolled. They
were randomized to receive BB (BB: 13 patients) or β-blockade and losartan (BB-L:
15 patients) for 35 months.
Results
In the BB-L group, aortic root dilation was reduced with treatment, and the annual
dilation rate of the aortic root was significantly lower than that of the BB group
(0.10 mm/yr vs 0.89 mm/yr; P=.02). The absolute aortic diameters at the sinus of Valsalva, annulus, and sinotubular
junction showed similar trends, with a reduced rate of dilation in the BB-L group
(P=.02, P=.03, and P=.03, respectively). Five patients (33%) treated with BB-L were noted to have a reduced
aortic root diameter. However, the differences between the groups regarding changes
in aortic stiffness and cross-sectional compliance were not statistically significant.
Conclusion
This randomized, open-label, active controlled trial mostly based on a pediatric population
demonstrated for the first time that losartan add-on BB therapy is safe and provides
more effective protection to slow the progression of aortic root dilation than does
BB treatment alone in patients with MFS.
Trial Registration
clinicaltrials.gov Identifier: NCT00651235.
Abbreviations and Acronyms:
ARB (angiotensin II receptor blockade), AT1 (angiotensin II type 1), BB (β-blockade), BB-L (BB and losartan), MFS (Marfan syndrome), TGF-β (transforming growth factor β)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Mayo Clinic ProceedingsAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- β-Blocker therapy does not alter the rate of aortic root dilation in pediatric patients with Marfan syndrome.J Pediatr. 2007; 150: 77-82
- The effect of β-blocker therapy on clinical outcome in patients with Marfan's syndrome: a meta-analysis.Int J Cardiol. 2007; 114: 303-308
- Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome.Science. 2006; 312: 117-121
- Latent transforming growth factor β-binding protein 1 interacts with fibrillin and is a microfibril-associated protein.J Biol Chem. 2003; 278: 2750-2757
- Angiotensin II blockade reverse myocardial fibrosis in a transgenic mouse model of human hypertrophic cardiomyopathy.Circulation. 2001; 103: 789-791
- Angiotensin II upregulates transforming growth factor-β type I receptor on rat vascular smooth muscle cells.Am J Hypertens. 2000; 13: 191-198
- Angiotensin II blockade and aortic-root dilation in Marfan's syndrome.N Engl J Med. 2008; 358: 2787-2795
- Revised diagnostic criteria for the Marfan syndrome.Am J Med Genet. 1996; 62: 417-426
- Screening for aortic root dilation in Marfan syndrome using the ratio of the aortic root to descending aortic diameters in children.J Am Soc Echocardiogr. 2009; 22: 1109-1113
- Theoretical and empirical derivation of cardiovascular allometric relationships in children.J Appl Physiol. 2005; 99: 445-457
- Evaluation of aortic insufficiency by Doppler color flow mapping.J Am Coll Cardiol. 1987; 9: 952-959
- Color Doppler assessment of mitral regurgitation with orthogonal planes.Circulation. 1987; 75: 175-183
- Presence of increased stiffness of the common carotid artery and endothelial dysfunction in severely obese children: a prospective study.Lancet. 2001; 358: 1400-1404
- Aortic stiffness as a risk factor for recurrent acute coronary events in patients with ischaemic heart disease.Eur Heart J. 2000; 21: 390-396
- The revised Ghent nosology for the Marfan syndrome.J Med Genet. 2010; 47: 476-485
- Effect of perindopril on large artery stiffness and aortic root diameter in patients with Marfan syndrome: a randomized controlled trial.JAMA. 2007; 298: 1539-1547
- Arterial hemodynamic indexes in Marfan's syndrome.Circulation. 1989; 79: 854-862
- Changes in aortic distensibility and pulse wave velocity assessed with magnetic resonance imaging following β-blocker therapy in the Marfan syndrome.Am J Cardiol. 1998; 82: 203-208
- Two-dimensional echocardiographic aortic root dimensions in normal children and adults.Am J Cardiol. 1989; 64: 507-512
Article Info
Publication History
Published online: January 14, 2013
Footnotes
Grant Support: This work was supported by a grant from the National Clinical Trial and Research Center of National Taiwan University Hospital ( NCTRC 200604 ).
Identification
Copyright
© 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.