Cytochrome P450 2C9 polymorphism and acenocoumarol therapy.

Abstract

BACKGROUND: Oral anticoagulants, in Hungary acenocoumarol being the one exclusively used, have a low therapeutic index and a high bleeding complication rate. The cytochrome P450 2C9 enzyme plays an important role in their metabolism. AIM: To investigate the influence of CYP2C9 polymorphism on the occurrence of bleeding complications related to acenocoumarol therapy. METHODS: Genotyping of 421 patients (183 men and 238 women, mean age 66.2+/-11.8 years), who had been taking acenocoumarol for at least 6 months, was performed. Based on patient history and laboratory data, the correlations between genotype and acenocoumarol dose and bleeding complications were retrospectively analysed. RESULTS: In 145 patients bearing alleles with reduced activity (CYP2C9*2 and/or *3), the optimal dose of acenocoumarol was significantly (p<0.001) lower than in patients with the wild type allele (2.12+/-0.96 mg/day and 2.90+/-1.46 mg/day, respectively). In comparison with wild type allele patients, the mean daily acenocoumarol dose was lower in the CYP2C9*2 group, and the lowest in *3 bearers. Although the occurrence of minor bleeding complications in patients with the variant allele was significantly (p <0.005) higher (OR=1.99 [CI: 1.20-3.33]) than in other patients, there was no difference in major bleeding complications. CONCLUSIONS: Patients bearing CYP2C9 alleles with reduced enzymatic activity have a lower acenocoumarol requirement. In patients with CYP2C9*2 and *3 alleles the frequency of minor bleeding complications and the occurrence of high INR values were significantly higher, but there was no difference in the rate of major bleedings.