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COMPARE: COMPARE: Effect of losartan on aortic dilatation rate in adults with Marfan Syndrome

Valvular Heart Diseases


Presenter abstract
Discussant report
All the Scientific resources on ESC Congress 365

Presentation

By Maarten Groenink
Other authors: MD Romy Franken, the Netherlands
MD Alexander den Hartog, the Netherlands
Background:
Patients with Marfan syndrome (MFS) have an increased risk of life-threatening aortic complications, mostly preceded by aortic dilatation. Recently, treatment with losartan showed reduction of the aortic dilatation rate in a MFS mouse model. The primary aim of our study was to determine whether losartan reduces aortic dilatation rate in humans with MFS.

Methods:
In this multicenter, open-label, randomized controlled trial with blinded assessments, losartan was compared with no additional treatment in 233 adults with MFS. The primary endpoint was aortic dilatation rate at any aortic level as determined by magnetic resonance imaging after 3 years of follow-up. The secondary endpoint was the reduction of the incidence of cardiovascular mortality, aortic dissection or prophylactic aortic surgery. The effect of losartan on aortic dilatation rate was evaluated by covariance analysis with baseline aortic dimension as covariate.

Results:
A total of 233 participants (47% female) underwent randomization to either losartan (n=116) or no additional treatment (n=117). Follow-up was 3.1±0.4 years, similar in both arms.
Further results will be submitted separately because the manuscript is currently under review by the New England Journal of Medicine.

Conclusions:
In this study we determined whether losartan treatment reduced aortic root dilatation rate in adult Marfan patients. Conclusion will be submitted separately.

Discussant Report

Pedro Trigo Trindade
In this HOTLINE session, Groenink et al (1) present the first prospective, multicentre, randomized, controlled trial indicating a beneficial effect of losartan in adults with Marfan syndrome (MFS).
COMPARE (COzaar in Marfan PAtients Reduces Aortic Enlargement) was designed to test the hypothesis of whether losartan reduces the aortic dilatation rate at any of six predefined aortic levels in adults with MFS. Additional aims of the study were to examine the effect of losartan on aortic volume and incidence of aortic dissection, on elective aortic surgery or cardiovascular death.
The authors enrolled 233 operated and unoperated patients who were randomized to losartan or no additional treatment. All previously prescribed medication, including beta-blockers and calcium channel blockers, was continued after inclusion. Importantly, by design the trial was open label with blinded assessment of endpoints. At baseline, patients would undergo magnetic resonance imaging (MRI) [or exceptionally computed tomography (CT)] of the entire aorta and again at 3 years of follow-up. Clinical assessment and transthoracic echocardiography were performed on an annual basis.
The authors were able to evaluate the aortic root dilatation rate in 145 patients with a native aortic root, and show that after 3 years of follow-up, the aortic root dilatation rate was significantly lower in the losartan group compared with the control group, with a number-needed-to-treat of 5.3 patients. Furthermore, in patients with prior aortic root replacement, aortic arch dilatation rate was significantly lower in the losartan group.
However, no significant differences in separate clinical endpoints or the composite clinical endpoint could be shown between groups.
In summary, according to the results of COMPARE addition of losartan to standard care in Marfan patients should be advised.
1 - Groenink M, den Hartog AW, Franken M, Radonic T, de Waard V, Timmermans J, Scholte AJ, van den Berg MP, Spijkerboer AM, Marquering HA, Zwinderman AH, Mulder BJM. Eur Heart J 2013;

References


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SessionTitle:

COMPARE: COMPARE: Effect of losartan on aortic dilatation rate in adults with Marfan Syndrome

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.