Losartan Versus Atenolol for Prevention of Aortic Dilation in Patients With Marfan Syndrome

J Am Coll Cardiol. 2018 Oct 2;72(14):1613-1618. doi: 10.1016/j.jacc.2018.07.052.

Abstract

Background: Beta-blockers are the standard treatment in Marfan syndrome (MFS). Recent clinical trials with limited follow-up yielded conflicting results on losartan's effectiveness in MFS.

Objectives: The present study aimed to evaluate the benefit of losartan compared with atenolol for the prevention of aortic dilation and complications in Marfan patients over a longer observation period (>5 years).

Methods: A total of 128 patients included in the previous LOAT (LOsartan vs ATenolol) clinical trial (64 in the atenolol and 64 in the losartan group) were followed up for an open-label extension of the study, with the initial treatment maintained.

Results: Mean clinical follow-up was 6.7 ± 1.5 years. A total of 9 events (14.1%) occurred in the losartan group and 12 (18.8%) in the atenolol group. Survival analysis showed no differences in the combined endpoint of need for aortic surgery, aortic dissection, or death (p = 0.462). Aortic root diameter increased with no differences between groups: 0.4 mm/year (95% confidence interval: 0.2 to 0.5) in the losartan and 0.4 mm/year (95% confidence interval: 0.3 to 0.6) in the atenolol group. In the subgroup analyses, no significant differences were observed considering age, baseline aortic root diameter, or type of dominant negative versus haploinsufficient FBN1 mutation.

Conclusions: Long-term outcome of Marfan syndrome patients randomly assigned to losartan or atenolol showed no differences in aortic dilation rate or presence of clinical events between treatment groups. Therefore, losartan might be a useful, low-risk alternative to beta-blockers in the long-term management of these patients.

Keywords: Marfan syndrome; aortic aneurysm; losartan.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-1 Receptor Antagonists / therapeutic use
  • Adult
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Aorta / diagnostic imaging*
  • Aorta / surgery
  • Aortic Aneurysm / etiology
  • Aortic Aneurysm / mortality
  • Aortic Aneurysm / prevention & control
  • Aortic Dissection / etiology
  • Aortic Dissection / mortality
  • Aortic Dissection / prevention & control
  • Atenolol / therapeutic use*
  • Dilatation, Pathologic / diagnostic imaging
  • Dilatation, Pathologic / etiology*
  • Dilatation, Pathologic / prevention & control*
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Losartan / therapeutic use*
  • Magnetic Resonance Imaging, Cine
  • Male
  • Marfan Syndrome / complications
  • Marfan Syndrome / drug therapy*
  • Marfan Syndrome / mortality
  • Young Adult

Substances

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