Features of warfarin dosage in the condition of polypharmacotherapy in patients after the prosthetic heart valve implantation

Authors: E.Z. Golukhova, S.M. Arslanbekova, D.A. Sychev, E.V. Kuznetsova

Company: 1 A.N. Bakoulev Scientific Center for Cardiovascular Surgery of Russian Academy of Medical Sciences;
2 Center for clinical pharmacology “Scientific Center for expertise of remedies for medical application” of Ministry
of Health of the Russian Federation

For citation: Golukhova EZ, Arslanbekova SM, Sychev DA, et al. Features of warfarin dosage in the condition of polypharmacotherapy in patients after the prosthetic heart valve implantation. Kreativnaya kardiologiya. 2013; 1: 58-65 (in Russian)

Keywords: prosthetic heart valve warfarin polymorphism of cytochrome P450 2C9 gene antibacterial medication amiodarone рrednisolone

Полнотекстовая версия:  



Objective. To study the impact of drug-drug interaction on the maintenance dose of warfarin in the early postoperative period in the condition of polypharmacotherapy.

Material and methods. The whole of 76 patients were included in the study, mean age 45±13 years. All patients underwent heart valve replacement. 2–4 days after surgery warfarin was administered for all patients according to the standard scheme 5mg/day under the control of the International normalized ratio (INR). In conjunction with warfarin patients received medication needed for prophylaxis and treatment of postoperative complications. CYP2C9 genotype bearing was determined with the technique of polymerase chain reaction with the restriction fragment length polymorphism (PCR–RFLP) assay after preliminary isolation of DNA from the whole blood.

Results. In the early postoperative period the chosen Warfarin doses were much lower from statistical standpoint than those in late postoperative period (4.4±1.8 mg vs. 5.6±2.1 mg, р=0.001). As a result of genotyping the statistically significant low therapeutic Warfarin doses were determined in patients with CYP2C9*1/*1 genotype who took amiodarone (4.4±1.8 mg vs. 5.5±2.1 mg, р=0.003) and prednisolone (3.6±1.5 mg vs. 5.1±1.9 mg, р=0.020). But patients with non-CYP2C9*1/*1 genotype did not show a statistically significant difference between the doses of warfarin.

Conclusion. Lower warfarin doses were associated only in patients with CYP2C9*1/*1 genotype, but not in patients bearing CYP2C9*2 and CYP2C9*3 genotypes (non-CYP2C9*1/*1 genotypes), who initially have had the genetically determined low CYP2C9 isoenzyme activity, which is already apparently not able for reduction under the influence of these inhibitors.


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Chief Editor

Leo A. Bockeria, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, Director of Bakoulev National Medical Research Center for Cardiovascular Surgery