Cytochrome P450 2C9 polymorphism and acenocoumarol therapy.

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.

[Treatment of atrial fibrillation in a Hungarian hospital department of cardiologic internal medicine at the turn of the millennium]. / Törekvés a pitvarfibrilláció ritmuskontroll-kezelésére kardiológiai profilú belgyógyászati osztályon az ezredfordulón.

INTRODUCTION: The atrial fibrillation is a severe and frequent disease, which influences greatly the patients' quality of life. Only a few Hungarian studies exist which discuss the physicians' own experiences in its treatment. AIM: The description of the experiences acquired in an internal medicine department with cardiological profile during the treatment based on the actual guidelines and the review of the results of one year follow-up. METHOD: Retrospective analysis of the data of patients treated with atrial fibrillation between 1 january 1999 and 31 december 2001 and a one year follow-up was performed. The age, gender, success in cardioversion, the antiarrhythmic therapy at the discharge and the modification in it during the first year were evaluated. RESULTS: During the 3 years long period 1115 patients with atrial fibrillation were admitted (53.9% female, 46.1% male, the mean age was 72.0 +/- 10.4 years), 391 of whom were discharged with sinus rhythm. In 193 cases (49%) a spontaneous cardioversion was observed. 120 electrical (31%) and 78 pharmacological (20%) cardioversions were performed. The electrical form was carried out in 42 cases with acute atrial fibrillation (in 36 of them successfully) and in 100 cases as an elective procedure, in 84 successfully. Pharmacological cardioversion was made in 39 acute cases with the administration of propafenone (in 29 ones successfully) and in 57 elective cases with quinidine + beta-blocker + magnesium (in 49 ones successfully). For the maintenance of sinus rhythm in the 38.8% of cases amiodarone, 24.0% propafenone, 19.9% sotalol, 10.7% beta-blocker, 0.8% quinidine, 0.5% prajmaline was administered, and 5.1% of the patients didn't receive any special treatment. During the one year follow-up from the 391 patients 261 remained on sinus rhythm, in 81 cases (21%) the return of the atrial fibrillation was diagnosed (in 57 of them a successful cardioversion was performed again), 11 patients (3%) died and 38 (9%) were lost for observation. At the time of the one year control 57.8% of patients treated with amiodarone, 61.7% of those treated with propafenone, 67.9% with sotalol and 35.7% with beta-blocker remained on sinus rhythm. The amiodarone was omitted in 17 cases because of its side effects. CONCLUSIONS: The treatment of the atrial fibrillation has to be performed individually taking into account the guidelines, the comorbidity, the time of the beginning of rhythm disorder, the patients' present other drugs and the former antiarrhythmic therapy. A continuous and consistent follow-up of these patients is crucial.