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Acenocoumarol stabilization is delayed in CYP2C93 carriers
Tom Schalekamp1, Johanna H H van Geest-Daalderop, Hanneke de Vries-Goldschmeding
1Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht University, Utrecht, The Netherlands. t.schalekamp@pharm.uu.nl
Clinical Pharmacology and Therapeutics
|April 30, 2004
Summary
The CYP2C9*3 gene variant is linked to difficulties achieving stable anticoagulation and increased overanticoagulation risk with acenocoumarol. CYP2C9 genotyping may help identify patients needing closer monitoring for acenocoumarol therapy.
Area of Science:
- Pharmacogenomics
- Clinical Pharmacology
- Genetics
Background:
- Acenocoumarol is a widely used anticoagulant.
- Achieving stable therapeutic anticoagulation can be challenging.
- Genetic variations, particularly in the cytochrome P450 (CYP) 2C9 gene, are known to influence drug metabolism and response.
Purpose of the Study:
- To investigate the association between CYP2C9 allelic variants and anticoagulation problems.
- To assess the impact of CYP2C9 genotypes on acenocoumarol treatment stability and safety within the first 3 to 6 months.
Main Methods:
- A prospective follow-up study conducted at two anticoagulation clinics in the Netherlands.
- Standard acenocoumarol dosing regimen initiated.
- CYP2C9 genotyping performed.
- International Normalized Ratio (INR), comedication, and comorbidity data collected.
Main Results:
- 231 subjects genotyped: 147 wild-type (CYP2C9*1/*1), 38 CYP2C9*2 carriers, 46 CYP2C9*3 carriers.
- CYP2C9*3 carriers showed a reduced likelihood of achieving stable anticoagulation (HR 0.62) and an increased risk of severe overanticoagulation (INR >6.0) (HR 3.80) compared to wild-type.
- No significant differences in outcomes were observed between CYP2C9*2 carriers and wild-type subjects.
Conclusions:
- CYP2C9*3 allele carriers experience greater challenges with acenocoumarol stabilization and are at higher risk of overanticoagulation.
- CYP2C9 genotyping can identify patients who may benefit from more frequent INR monitoring.
- Personalized anticoagulation management based on CYP2C9 genotype may improve acenocoumarol therapy outcomes.