Effect van behandeling met losartan op aortadilatatie bij volwassenen met het Marfan-syndroom*

Objective

To determine the effect of losartan on aortic dilatation rate in adults with Marfan syndrome.

Design

Randomised, controlled multicentre clinical trial.

Method

Adult Marfan patients from the 4 Marfan centres in the Netherlands with a maximum of 1 aortic prosthesis were randomised to 100 mg losartan once daily or no additional losartan treatment. All patients continued their standard treatment, which consisted mainly of β-blockers. The primary outcome measure was a reduction in aortic dilatation rate. The secondary outcome measures were an increase in aortic volume and the incidence of the combined outcome measure: cardiovascular mortality, aortic dissection and aorta surgery. This trial was registered with the Dutch Trial Register (NTR1423).

Results

233 patients were included. Absolute aortic diameters were measured at the beginning and at the end of the study. The aortic root dilatation rate after 3 years was significantly lower in patients in the losartan group than in those in the control group (0.77 mm/3 years (SD: 1.36) vs. 1.35 mm/3 years (SD: 1.55); p = 0.014). The dilatation rate in the trajectory beyond the aortic root was comparable in the two groups. There were no differences in the secondary outcome measures between the two groups. A subanalysis of patients with aortic root replacement surgery prior to inclusion in the study demonstrated that in this group losartan treatment led to a significant decrease in aortic arch dilatation rate versus standard treatment (0.50 mm/3 years (SD: 1.26) vs. 1.01 mm/3 years (1.31); p = 0.033).

Conclusion

In adult Marfan patients, losartan treatment reduces the aortic root dilatation rate. After aortic root surgery, losartan treatment reduces dilatation rate of the aortic arch.

Conflict of interest and financial support: disclosure forms provided by the authors are available along with the full text of this article at www.ntvg.nl, search for A6845; click on ‘Belangenverstrengeling’ (‘Conflict of interest’). This study was financed by a subsidy from the Nederlandse Hartstichting(Dutch Heart Foundation) (2008B115)and supported by the Interuniversitair Cardiologisch Instituut Nederland(ICIN)(Interuniversity Cardiology Institute for the Netherlands).