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Cytochrome P450 2C9 polymorphism and acenocoumarol therapy
Laszlo Mark1, Janos Marki-Zay, Lajos Fodor
12nd Department of Internal Medicine--Cardiology, Pandy Kalman Bekes County Hospital, Semmelweis u. 1., P.O. Box 46., H-5700 Gyula, Hungary. mark@pandy.hu
Kardiologia Polska
|May 16, 2006
Summary
Patients with reduced CYP2C9 enzyme activity require lower acenocoumarol doses. While minor bleeding risks increase with CYP2C9*2 and *3 alleles, major bleeding rates remain unchanged.
Area of Science:
- Pharmacogenomics
- Clinical Pharmacology
- Internal Medicine
Background:
- Acenocoumarol, a widely used oral anticoagulant in Hungary, has a narrow therapeutic index and a high risk of bleeding complications.
- The cytochrome P450 2C9 (CYP2C9) enzyme is crucial for the metabolism of acenocoumarol.
Purpose of the Study:
- To investigate the impact of CYP2C9 genetic variations on acenocoumarol therapy outcomes.
- To determine the relationship between CYP2C9 genotype and the incidence of bleeding complications.
Main Methods:
- Genotyping was performed on 421 patients undergoing long-term acenocoumarol treatment.
- Retrospective analysis correlated patient genotype with prescribed acenocoumarol dosage and bleeding events.
Main Results:
- Patients with reduced-activity CYP2C9 alleles (*2 and/or *3) required significantly lower acenocoumarol doses (2.12 mg/day) compared to wild-type patients (2.90 mg/day).
- The incidence of minor bleeding complications was significantly higher in patients with variant CYP2C9 alleles (OR=1.99).
- No significant difference was observed in the rate of major bleeding complications between genotype groups.
Conclusions:
- CYP2C9 polymorphism influences acenocoumarol dosage requirements, with reduced activity alleles necessitating lower doses.
- Variant CYP2C9 alleles (*2, *3) are associated with an increased frequency of minor bleeding and elevated INR values.
- The rate of major bleeding complications does not differ significantly based on CYP2C9 genotype.