Long-term anticoagulant effects of the CYP2C9 and VKORC1 genotypes in acenocoumarol users


Anke-Hilse Maitland-van der Zee, Division of Pharmacoepidemiology & Clinical Pharmacology, Faculty of Science, Utrecht University, PO Box 80 082, 3508 TB Utrecht, the Netherlands.
Tel.: +31 622 736 715; fax: +31 30 253 9166.
E-mail: a.h.maitland@uu.nl


Summary.  Background:  The required acenocoumarol dose and the risk of underanticoagulation and overanticoagulation are associated with the CYP2C9 and VKORC1 genotypes. However, the duration of the effects of these genes on anticoagulation is not yet known.

Objectives:  In the present study, the effects of these polymorphisms on the risk of underanticoagulation and overanticoagulation over time after the start of acenocoumarol were investigated.

Patients/methods:  In three cohorts, we analyzed the relationship between the CYP2C9 and VKORC1 genotypes and the incidence of subtherapeutic or supratherapeutic International Normalized Ratio (INR) values (< 2 and > 3.5) or severe overanticoagulation (INR > 6) for different time periods after treatment initiation.

Results:  Patients with polymorphisms in CYP2C9 and VKORC1 had a higher risk of overanticoagulation (up to 74%) and a lower risk of underanticoagulation (down to 45%) in the first month of treatment with acenocoumarol, but this effect diminished after 1–6 months.

Conclusions:  Knowledge of the patient’s genotype therefore might assist physicians to adjust doses in the first month(s) of therapy.