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 receivingBB (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.
RCT Entities:
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.
Authors: Syed Usman Bin Mahmood; Camilo A Velasquez; Mohammad A Zafar; Ayman A Saeyeldin; Adam J Brownstein; Bulat A Ziganshin; John A Elefteriades; Sandip K Mukherjee Journal: Ann Cardiothorac Surg Date: 2017-11
Authors: Ronald V Lacro; Harry C Dietz; Lynn A Sleeper; Anji T Yetman; Timothy J Bradley; Steven D Colan; Gail D Pearson; E Seda Selamet Tierney; Jami C Levine; Andrew M Atz; D Woodrow Benson; Alan C Braverman; Shan Chen; Julie De Backer; Bruce D Gelb; Paul D Grossfeld; Gloria L Klein; Wyman W Lai; Aimee Liou; Bart L Loeys; Larry W Markham; Aaron K Olson; Stephen M Paridon; Victoria L Pemberton; Mary Ella Pierpont; Reed E Pyeritz; Elizabeth Radojewski; Mary J Roman; Angela M Sharkey; Mario P Stylianou; Stephanie Burns Wechsler; Luciana T Young; Lynn Mahony Journal: N Engl J Med Date: 2014-11-18 Impact factor: 91.245