Key result
The ABCB1 rs4148738 CT genotype was associated with a significantly higher residual equilibrium concentration of rivaroxaban compared to the CC genotype (P=0.039).
Why the study?
Evaluating ABCB1 and CYP3A4/3A5 gene polymorphisms is promising for understanding prothrombin time variability, DOAC residual concentrations, and developing personalized anticoagulation approaches in atrial fibrillation.
Do ABCB1 and CYP3A4/3A5 gene polymorphisms affect prothrombin time and residual equilibrium concentration of rivaroxaban in patients with non-valvular atrial fibrillation?
Observational (n=86)
Do ABCB1 and CYP3A4/3A5 gene polymorphisms affect prothrombin time and residual equilibrium concentration of rivaroxaban in patients with non-valvular atrial fibrillation?
p-value: p=0.039
The ABCB1 rs4148738 CT genotype is associated with significantly higher residual equilibrium concentrations of rivaroxaban compared to the CC genotype in patients with atrial fibrillation, highlighting a potential pharmacogenetic influence on drug levels.
Hypothesis-generating for ABCB1-guided rivaroxaban dosing; should not yet change practice without prospective validation.
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.
No takes yet. Share an insight, caveat, or question.
Sychev et al. (2022) conducted an observational in non-valvular atrial fibrillation (n=86). ABCB1 rs4148738 CT genotype vs. ABCB1 rs4148738 CC genotype was evaluated on residual equilibrium concentration of rivaroxaban (p=0.039). The ABCB1 rs4148738 CT genotype was associated with a significantly higher residual equilibrium concentration of rivaroxaban compared to the CC genotype (P=0.039).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: