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Losartan Added to β-Blockade Therapy for Aortic Root Dilation in Marfan Syndrome: A Randomized, Open-Label Pilot Study

Published:January 14, 2013DOI:https://doi.org/10.1016/j.mayocp.2012.11.005

      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

      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)
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