Long-term anticoagulant effects of the CYP2C9 and VKORC1 genotypes in acenocoumarol users
Publication date
2012-04
Authors
Verhoef, Talitha I.
Redekop, W K
Buikema, M M
Schalekamp, Tom
van der Meer, Freek
Le Cessie, S
Wessels, J A M
van Schie, Rianne M. F.
De Boer, Anthonius
Teichert, M
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Document Type
Article
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Abstract
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.
Keywords
Acenocoumarol, Aged, Anticoagulants, Aryl Hydrocarbon Hydroxylases, Blood Coagulation, Cytochrome P-450 CYP2C9, Drug Administration Schedule, Drug Dosage Calculations, Drug Monitoring, Female, Gene Frequency, Genotype, Humans, International Normalized Ratio, Male, Medication Errors, Mixed Function Oxygenases, Netherlands, Pharmacogenetics, Phenotype, Polymorphism, Genetic, Predictive Value of Tests, Risk Assessment, Risk Factors, Time Factors, Vitamin K Epoxide Reductases
Citation
Verhoef, T I, Redekop, W K, Buikema, M M, Schalekamp, T, Van Der Meer, F J M, Le Cessie, S, Wessels, J A M, Van Schie, R M F, De Boer, A, Teichert, M, Visser, L E, Maitland-Van Der Zee, A H & EU-PACT Group 2012, 'Long-term anticoagulant effects of the CYP2C9 and VKORC1 genotypes in acenocoumarol users', Journal of Thrombosis and Haemostasis, vol. 10, no. 4, pp. 606-614. https://doi.org/10.1111/j.1538-7836.2012.04633.x