Influence of ABCB1, CYP3A5 and CYP3A4 gene polymorphisms on prothrombin time and the residual equilibrium concentration of rivaroxaban in patients with non-valvular atrial fibrillation in real clinical practice.

OBJECTIVE

The study of ABCB1 and CYP3A4/3A5 gene polymorphism genes is promising in terms of their influence on prothrombin time variability, the residual equilibrium concentration of direct oral anticoagulants (DOACs) in patients with atrial fibrillation and the development of new personalized approaches to anticoagulation therapy in these patients. The aim of the study is to evaluate the effect of ABCB1 (rs1045642) C>T; ABCB1 (rs4148738) C>T and CYP3A5 (rs776746) A>G, CYP3A4*22(rs35599367) C>T gene polymorphisms on prothrombin time level and residual equilibrium concentration of rivaroxaban in patients with atrial fibrillation.

METHODS

In total 86 patients (42 men and 44 female), aged 67.24 ± 1.01 years with atrial fibrillation were enrolled in the study. HPLC mass spectrometry analysis was used to determine rivaroxaban residual equilibrium concentration. Prothrombin time data were obtained from patient records.

RESULTS

The residual equilibrium concentration of rivaroxaban in patients with ABCB1 rs4148738 CT genotype is significantly higher than in patients with ABCB1 rs4148738 CC (P  = 0.039). The analysis of the combination of genotypes did not find a statistically significant role of combinations of alleles of several polymorphic markers in increasing the risk of hemorrhagic complications when taking rivaroxaban.

CONCLUSION

Patients with ABCB1 rs4148738 CT genotype have a statistically significantly higher residual equilibrium concentration of rivaroxaban in blood than patients with ABCB1 rs4148738 CC genotype, which should be considered when assessing the risk of hemorrhagic complications and risk of drug-drug interactions. Further studies of the effect of rivaroxaban pharmacogenetics on the safety profile and efficacy of therapy are needed.