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

• Published in: Mayo Clinic proceedings Vol. 88; no. 3; pp. 271 - 276
• Main Authors: Chiu, Hsin-Hui, Wu, Mei-Hwan, Wang, Jou-Kou, Lu, Chun-Wei, Chiu, Shuenn-Nan, Chen, Chun-An, Lin, Ming-Tai, Hu, Fu-Chang
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.03.2013; Elsevier, Inc
• Subjects: Adolescent; Adrenergic beta blockers; Adrenergic beta-1 Receptor Antagonists - therapeutic use; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Aortic Diseases - drug therapy; Aortic Diseases - etiology; Atenolol - therapeutic use; Child; Dilatation, Pathologic - drug therapy; Dilatation, Pathologic - etiology; Drug Administration Schedule; Drug therapy; Drug Therapy, Combination; Female; Follow-Up Studies; Health aspects; Humans; Internal Medicine; Losartan; Losartan - therapeutic use; Male; Marfan syndrome; Marfan Syndrome - complications; Pilot Projects; Propranolol - therapeutic use; Treatment Outcome; Young Adult; United States; BB; ARB; BB-L; TGF-β; MFS; AT1; angiotensin II receptor blockade; BB and losartan; transforming growth factor β; AT 1; angiotensin II type 1; β-blockade; Marfan syndrome
• ISSN: 0025-6196; 1942-5546; 1942-5546
• DOI: 10.1016/j.mayocp.2012.11.005

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). 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. 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. 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. clinicaltrials.gov Identifier: NCT00651235.