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

Objective: To assess the tolerability and efficacy of the investigational use of the angiotensin II receptor blocker losartan added to beta-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 beta-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. (C) 2013 Mayo Foundation for Medical Education and Research square Mayo Clin Proc. 2013; 88(3): 271-276