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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

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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 (Cmin,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 Cmin,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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Authors and Affiliations

  1. Department of Clinical Pharmacology and Therapy, Russian Medical Academy of Continuous Professional Education, 2/1 Barrikadnaya St., Moscow, 123242, Russian Federation

    Dmitry Sychev, Olga Ostroumova, Karin Mirzaev, Sherzod Abdullaev, Natalia Denisenko, Zhannet Sozaeva & Anastasia Kachanova

  2. Department of Internal and Preventive Medicine, Central State Medical Academy of the Presidential Administration of the Russian Federation, Marshal Timoshenko Street, 19, Building 1A, Moscow, 121359, Russian Federation

    Marina Cherniaeva

  3. State Budgetary Institution of Health “Hospital for War Veterans No. 2” of the Department of Health of Moscow, Volgogradskiy Prospekt, 168, Moscow, 109472, Russian Federation

    Marina Cherniaeva, Svetlana Gorbatenkova & Vera Shastina

  4. Lomonosov Moscow State University Medical Research and Educational Center, 27\10, Lomonosovskiy Prospekt, Moscow, 119991, Russian Federation

    Nataliia Shakhgildian

  5. Research Center for Medical Genetics, 1 Moskvorechye st., Moscow, 115522, Russian Federation

    Karin Mirzaev

  6. Department of Therapy and Polymorbid Pathology, Russian Medical Academy of Continuous Professional Education, 2/1 Barrikadnaya St., Moscow, 123242, Russian Federation

    Olga Ostroumova

  7. Department of Personalized Medicine, Research Institute of Molecular and Personalized Medicine, Russian Medical Academy of Continuous Professional Education, 7/2 2nd Bokinskiy Drive, Moscow, 125284, Russian Federation

    Karin Mirzaev, Natalia Denisenko & Zhannet Sozaeva

  8. Department of Molecular Medicine, Research Institute of Molecular and Personalized Medicine, Russian Medical Academy of Continuous Professional Education, 7/2 2nd Bokinskiy Drive, Moscow, 125284, Russian Federation

    Sherzod Abdullaev & Anastasia Kachanova

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  1. Dmitry Sychev
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Correspondence to Marina Cherniaeva.

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Funding

This study was supported by Russian Science Foundation, project no. 22-15-0025 Personalized use of direct oral anticoagulants based on the pharmacogenomic approach. 2022 Competition for Grants in the area of “Conducting fundamental scientific research and exploratory research by individual research groups”.

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethics approval

The study was approved by the Ethics Committee of the Russian Medical Academy of Continuous Professional Education of the Ministry of Healthcare of the Russian Federation (Study Protocol No. 1, 22.01.2019) and it was carried out in accordance with the latest edition of the Declaration of Helsinki and the principles of Good Clinical Practice.

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Oral and written informed consent was obtained from all participants included in the study.

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Author contributions

Conceptualization: Dmitry Sychev, Olga Ostroumova, Marina Cherniaeva; Methodology: Dmitry Sychev, Olga Ostroumova, Marina Cherniaeva; Supervision: Dmitry Sychev, Olga Ostroumova; Formal Analysis: Marina Cherniaeva, Nataliia Shakhgildian; Funding Acquisition: Dmitry Sychev; Investigation: Marina Cherniaeva, Nataliia Shakhgildian, Karin Mirzaev, Sherzod Abdullaev, Natalia Denisenko, Zhannet Sozaeva, Anastasia Kachanova; Resources: Dmitry Sychev, Marina Cherniaeva, Karin Mirzaev, Sherzod Abdullaev, Natalia Denisenko, Zhannet Sozaeva, Anastasia Kachanova, Vera Shastina, Svetlana Gorbatenkova; Project Administration: Dmitry Sychev, Olga Ostroumova; Writing: Marina Cherniaeva, Nataliia Shakhgildian, Karin Mirzaev, Sherzod Abdullaev, Natalia Denisenko, Zhannet Sozaeva, Anastasia Kachanova, Vera Shastina, Svetlana Gorbatenkova; Review and Editing: Dmitry Sychev, Olga Ostroumova.

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Sychev, D., Ostroumova, O., Cherniaeva, M. et al. The Influence of ABCB1 (rs1045642 and rs4148738) Gene Polymorphisms on Rivaroxaban Pharmacokinetics in Patients Aged 80 Years and Older with Nonvalvular Atrial Fibrillation. High Blood Press Cardiovasc Prev 29, 469–480 (2022). https://doi.org/10.1007/s40292-022-00536-3

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