Losartan added to β-blockade therapy for aortic root dilation in Marfan syndrome: a randomized, open-label pilot study

Mayo Clin Proc. 2013 Mar;88(3):271-6. doi: 10.1016/j.mayocp.2012.11.005. Epub 2013 Jan 12.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • 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, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Losartan / therapeutic use*
  • Male
  • Marfan Syndrome / complications*
  • Pilot Projects
  • Propranolol / therapeutic use*
  • Treatment Outcome
  • Young Adult


  • Adrenergic beta-1 Receptor Antagonists
  • Angiotensin II Type 1 Receptor Blockers
  • Atenolol
  • Propranolol
  • Losartan

Associated data

  • ClinicalTrials.gov/NCT00651235