Artery Research (Dec 2009)

3.3 EFFECT OF CELIPROLOL ON PREVENTION OF CARDIOVASCULAR EVENTS IN VASCULAR EHLERS-DANLOS SYNDROME

  • K.T. Ong,
  • J. Perdu,
  • H. Plauchu,
  • J. De Backer,
  • A. De Paepe,
  • J. Emmerich,
  • X. Jeunemaitre,
  • D. Germain,
  • P. Collignon,
  • G. Georgesco,
  • E. Bozec,
  • J.S. Hulot,
  • S. Laurent,
  • P. Boutouyrie

DOI
https://doi.org/10.1016/j.artres.2009.10.154
Journal volume & issue
Vol. 3, no. 4

Abstract

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Background: Vascular Ehlers-Danlos syndrome (vEDS) is a rare severe genetic disease which results from mutations in the gene encoding type III procollagen (COL3A1), characterized by vascular and/or hollow organic ruptures. No treatment is yet validated. We tested the ability of celiprolol, a beta1-adrenoceptor antagonist with a beta2-adrenoceptor agonist action, for preventing the complications of vEDS in a prospective, randomized, open, blinded endpoints trial. Methods: Fifty three previously untreated vEDS patients were randomized to a 5-year treatment with either celiprolol (n=25) or no treatment (n=28). The two groups were matched for demographic, medical historic and clinical characteristics. Celiprolol was up-titrated from 100 to 400mg by steps of 100mg every 6 months. The primary end-point was an arterial event (rupture or dissection, fatal or not) occurring during follow-up. Secondary endpoints were intestinal or uterine rupture or major clinical events, related to vEDS, judged by the event committee. Results: Mean duration of follow-up was 47 (± 15) months. The study was ended prematurely by the safety monitoring board since significant differences were reached between two groups. The primary endpoint was reached by 5 patients (20%) in the celiprolol group and by 14 patients (50%) in the control group (hazard ratio, 0.36; 95% CI, 0.15 to 0.88; P=0.04). Primary plus secondary endpoints occurred in 6 patients (24%) in the celiprolol group and in 17 patient (61%) in the control group (hazard ratio, 0.31; 95% CI, 0.14 to 0.71; P=0.0097). Conclusions: Celiprolol effectively reduced both vascular complications and organic ruptures in vEDS patients.