Advances in basic and translational research have resulted in a better understanding of Marfan syndrome. Mouse studies have shown that medications such as angiotensin II receptor blockers (ARBs) can slow the enlargement of the aorta. Based on this understanding, eight prospective randomized controlled clinical trials were initiated to evaluate the effect of ARBs compared with traditional standard of care, beta blockers (BB) on aortic enlargement. Each of the trials had different formats such differences in the number of patients enrolled, different drug and dosage treatments and different control groups. These studies were designed to answer a number of important questions regarding the effectiveness, safety, and tolerability of ARB’s and BB’s. A summary of the trial’s structures are shown in table 1 and are listed according the date of publication. There are three additional trials in Belgium, Italy and the United Kingdom that have not yet published their results.

Taiwan Trial Summary

  • 28 Patients
  • Single center
  • Average Age: 13.1 years old + 6.3 years.
  • Aortic root z-score greater than 2.0 to participate
  • Follow-up: 35 months
  • Two test groups:
    • Group I: combination therapy of atenolol or propranolol (50 mg atenolol per day or 20 mg propranolol per day) combined with losartan which was uptitrated to the maximum tolerable dose of 100mg/day for adults and 50 mg/day for children.
    • Group 2: beta-blocker only at the maximum dose of 150mg/d for adults and 2mg/kg/d for children.
  • The combination therapy group had a larger aortic root dimension at the start of the trial 3.43 + 0.69 cm vs. 3.14 + 0.47 cm.

Results: The rate of growth was reduced in those who received combination therapy and there was a slight decrease in the aortic root z-score, while there was a slight increase in the z-score in the beta blocker group.


The Netherlands

  • 233 patients greater than 18 years old with some patients having previous aortic root replacement surgery
  • Multi-center trial
  • Follow-up: 3.1 + 0.4 years
  • Two groups:
    • Group 1 - Control Group - continue previous therapy
      • (70% BB, 2.6% CCB, calcium channel blocker: doses not reported)
      • 63 patients in this group had previous aortic root replacement
      • average age 38.3 + 13.4 yrs
      • aortic root dimension at enrollment was 43.7 + 4.8 mm
    • Group 2 - Losartan Group (up to 100 mg/d) plus previous therapy
      • (75% BB, 1.7% CCB; doses not reported)
      • 27 patients in this group had prior aortic root replacement
      • average age 36.8 + 12.3 yrs
      • Aortic root dimension at enrollment was 44.8 + 5.6 mm


  • Rate of aortic root dilation could only be assessed in 145 subjects who had not undergone surgery
  • Aortic root dilatation rate according to MRI and TEE was lower in the losartan group
  • There was no difference in the rate of growth at the ascending aorta, aortic arch and descending aorta levels
  • In those patients with aortic root replacement, the aortic arch dilatation rate according to MRI was lower in the losartan group, however there was no difference in the aortic dilatation rate according to MRI at the descending aorta level.



  • 303 patients
  • Multi-center
  • Average aortic root diameter at trial start was 39.2 + 5.8 mm but aortic enlargement was not required
  • Follow-up: 3.5 years
  • Average age was 29.9 years old, with 84 patients between 10 and 18 years old.
  • Two groups:
    • Group 1: Prior Therapy Only, also known as placebo group.
      • 86% received atenolol at an average dose of 65 mg while the other 14% received other drugs which were not specified.
    • Group 2: Prior Therapy plus losartan.
      • Losartan was given at a dose of 50 mg when patient was less than 110 lbs (22 patients) or 100 mg for those over the 110 lbs (129 patients).


  • The annual average z-score change was not significantly different in the two groups.
  • The systolic and diastolic blood pressures were lower in the losartan group.
  • Gene mutations of the patient population: It was found that 66 of the patients included in the trial or 22% had mutations in other genes than FBN-1.


United States

  • 608 patients
  • Multi-center
  • Follow-up: 3 years
  • Aortic root diameter at start of trial: z-score of 3 or above
  • Age range: 6 months - 25 years
  • Two groups:
    • Group 1: Atenolol Only
      • Dosage: from 0.5 mg/kg/day to 4 mg/kg/day, up to 250 mg resulting in some cases 2x the FDA recommended dose. Each patient’s heart rate was monitored and when there was a 20% decrease in heart rate during a 24 hour period, that indicated that the appropriate patient specific dose was reached. This is referred to as “titration to a hemodynamic effect.” As a result of this titration, each patient received the patient specific amount of drug so that each patient had the same controlled effect on their heart rate to eliminate this as a variable.
      • Average age: 11.5 + 6.5 years
    • Group 2: Losartan Only
      • Dosage: from 0.4 mg/kg/day and increased based on weight to a maximum dose up to 1.4 mg/kg/day, not to exceed 100 mg which is the FDA recommended dose.
      • Average age: 11.0 + 6.2 years


  • In Group 1, atenolol , given at a standardized hemodynamic doses which resulted in some cases being 2x the FDA recommended dose, was also able to reduce aortic z-score over the three year period.
  • In Group 2, losartan, at the FDA recommended dose, was able to reduce aortic z-score over the three year period.
  • Younger subjects showed a greater decrease in the aortic root z-score over time in both treatment groups.


Spain Trial Summary

  • 140 Patients
  • Two centers
  • Ages 5-60 years old with an average age of 25.2 + 13.7 years.
  • Aortic root z-score less than 4.5 cm to participate
  • Follow-up: 36 months
  • Two test groups:
    • Group I: Losartan at 1.4mg/kg/day with maximum set at 100mg/day
    • Group 2: Atenolol at 1.4mg/kg/day with maximum set at 100mg/day


  • Changes in the aortic root after 3 years of treatment did not differ significantly between treatment groups.



Several older and smaller trials were also performed as well as indicated by the references below:


  1. Shores J, Berger KR, Murphy EA, Pyeritz RE. Progression of aortic dilatation and the benefit of long-term beta-adrenergic blockade in Marfan’s syndrome. N Engl J Med 1994;330:1335-41.
  2. Brooke BS, Habashi JP, Judge DP, Patel N, Loeys B and Dietz HC. Agniotensin II blockage iand aortic-root-dilation in Marfan’s syndrome N Engl J Med 2008;358:2787-2795.
  3. Rossi-Foulkes R, Roman MJ, Rosen SE, et al. Phenotypic features and impact of beta blocker or calcium antagonist therapy on aortic lumen size in the Marfan syndrome. Am J Cardiol 1999;83:1364-8.
  4. Ladouceur M, Fermanian C, Lupoglazoff JM, et al. Effect of betablockade on ascending aortic dilatation in children with the Marfan syndrome. Am J Cardiol 2007;99:406-9.
  5. Selamet Tierney ES, Feingold B, Printz BF, et al. Beta-blocker therapy does not alter the rate of aortic root dilation in pediatric patients with Marfan syndrome. J Pediatr 2007;150:77-82.
  6. Pees C, Laccone F, Hagl M, et al. Usefulness of losartan on the size of the ascending aorta in an unselected cohort of children, adolescents, and young adults with Marfan syndrome. Am J Cardiol 2013;112: 1477-83.
  7. Mueller GC, Stierle L, Stark V, et al. Retrospective analysis of the effect of angiotensin II receptor blocker versus beta-blocker on aortic root growth in paediatric patients with Marfan syndrome. Heart 2014;100:214-8.
  8. Bhatt AB, Buck JS, Zuflacht JP, et al. Distinct effects of losartan and atenolol on vascular stiffness in Marfan syndrome. Vasc Med 2015;20:317-25.
  9. Sandor GG, Alghamdi MH, Raffin LA, et al. A randomized, double blind pilot study to assess the effects of losartan vs. atenolol on the biophysical properties of the aorta in patients with Marfan and Loeys-Dietz syndromes. Int J Cardiol 2015;179:470-5.