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4 ème Journée et Prix de la Recherche Clinique – 19 mai 2011 Présentations posters
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P24a
IMPACT OF CYP2C9 POLYMORPHIMS AND/OR INHIBITORS ON THE RISK OF
OVERANTICOAGULATION IN PATIENTS STARTING AN ACENOCOUMAROL TREATMENT
L. Gschwind1, V. Rollason Gumprecht1, P. Bonnabry2, F. Boehlen3, P. de Moerloose3, C.
Combescure4, M. Rebsamen5, P. Dayer1, J. Desmeules1
1 Division of clinical pharmacology and toxicology, 2 Sector of clinical pharmacy, Division of clinical pharmacology
and toxicology 3 Division of angiology and hemostasis, 4 Division of clinical epidemiology, 5 Division of laboratory
medicine, University Hospitals of Geneva, Switzerland
Introduction: Acenocoumarol is an oral anticoagulant commonly prescribed in Switzerland. As
warfarin, the response to treatment varies widely and is affected by genetic and environmental factors,
bleeding being the most frequent serious adverse event. Drug-drug interactions (DDIs) or CYP2C9
polymorphisms are among the factors known to affect the risk of overanticoagulation. The objective of
this study was to investigate the impact of CYP2C9 polymorphisms and drug interactions on
overanticoagulation risk in patients treated with acenocoumarol.
Méthode: A prospective observational study was performed on patients starting acenocoumarol.
CYP2C9 genotypes were assessed and data on INR, comedications, comorbidities, and doses of
acenocoumarol were collected during the first 35 days of therapy. Drugs known to inhibit CYP2C9
were considered as relevant DDIs. Overanticoagulation was defined as the occurrence of at least one
INR≥4.
Résultats: The CYP2C9 genotype of 107 subjects was assessed: 63.5% were wild-type subjects,
26.2% were carriers of CYP2C9*2 and 10.3% of CYP2C9*3. 42.1% had at least one INR≥4. Patients
taking CYP2C9 inhibitors (31%) had an increased risk of overanticoagulation (p