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High Blood Pressure & Cardiovascular Prevention

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01.09.2022 | Original article

The Influence of ABCB1 (rs1045642 and rs4148738) Gene Polymorphisms on Rivaroxaban Pharmacokinetics in Patients Aged 80 Years and Older with Nonvalvular Atrial Fibrillation

verfasst von: Dmitry Sychev, Olga Ostroumova, Marina Cherniaeva, Nataliia Shakhgildian, Karin Mirzaev, Sherzod Abdullaev, Natalia Denisenko, Zhannet Sozaeva, Anastasia Kachanova, Svetlana Gorbatenkova, Vera Shastina

Erschienen in: High Blood Pressure & Cardiovascular Prevention | Ausgabe 5/2022

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Abstract

Introduction

ABCB1 gene polymorphisms are associated with rivaroxaban distribution changes and adverse reactions but the data are controversial.

Aim

To evaluate the influence of ABCB1 (rs1045642 and rs4148738) gene polymorphisms on rivaroxaban pharmacokinetics in patients aged 80 years and older with nonvalvular atrial fibrillation (NAF).

Methods

128 patients aged 80 years and older (median [Me] age 87.5 [83.0–90.0] years) with NAF were included. We performed ABCB1 (rs1045642 and rs4148738) genotyping, measured the trough steady-state plasma concentration (C_min,ss) of rivaroxaban and prothrombin time (PT) and analyzed prior medical records for clinically relevant non-major bleeding (CRNMB).

Results

CC genotype carriers had no differences in C_min,ss (p > 0.05) compared with the CT and TT rs1045642 and rs4148738 genotypes carriers. CC genotype carriers had no differences in PT (p > 0.05) compared with the CT rs1045642 and rs4148738 and TT rs4148738 genotypes carriers. In the TT genotype PT levels were higher than in the CC rs1045642 genotype: Me 14.2 [13.0–16.1] sec vs 13.3 [12.4–14.5] sec (p = 0.049). Incidence of CRNMB was higher in patients with the TT genotype compared with the CC rs1045642 (29.3% vs 4.5%, p = 0.021) and rs4148738 (39.3% vs 8.1%, p = 0.008) and the CT genotype rs4148738 (39.3% vs 14.3%, p = 0.002).

Conclusion

ABCB1 (rs1045642 and rs4148738) polymorphisms didn’t influence rivaroxaban pharmacokinetics in patients aged 80 years and older with NAF. TT carriers developed CRNMB more frequently compared with the CC rs1045642 and the CC and CT rs4148738 genotypes. The haplotype TT–TT haplotype was associated with a higher frequency of CRNMB.

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Titel: The Influence of ABCB1 (rs1045642 and rs4148738) Gene Polymorphisms on Rivaroxaban Pharmacokinetics in Patients Aged 80 Years and Older with Nonvalvular Atrial Fibrillation
verfasst von: Dmitry Sychev
Olga Ostroumova
Marina Cherniaeva
Nataliia Shakhgildian
Karin Mirzaev
Sherzod Abdullaev
Natalia Denisenko
Zhannet Sozaeva
Anastasia Kachanova
Svetlana Gorbatenkova
Vera Shastina
Publikationsdatum: 01.09.2022
Verlag: Springer International Publishing
Erschienen in: High Blood Pressure & Cardiovascular Prevention / Ausgabe 5/2022
Print ISSN: 1120-9879
Elektronische ISSN: 1179-1985
DOI: https://doi.org/10.1007/s40292-022-00536-3

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The Influence of ABCB1 (rs1045642 and rs4148738) Gene Polymorphisms on Rivaroxaban Pharmacokinetics in Patients Aged 80 Years and Older with Nonvalvular Atrial Fibrillation

Abstract

Introduction

Aim

Methods

Results

Conclusion

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Abstract

Introduction

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Methods

Results

Conclusion

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