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

Sychev, D. A.; Остроумова, О. Д.; Chernyaeva, M. S.; Shakhgildian, Nataliia; Мирзаев, К. Б.; Abdullaev, Sh. P.; Denisenko, Natalia P.; Созаева, Ж. А.; Качанова, А. А.; Gorbatenkova, Svetlana; Shastina, Vera

doi:10.1007/s40292-022-00536-3

Cited by 10 publications

(15 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…All three were homozygous mutations (rs1045642:TT, rs1128503:TT, rs2032582:TT). A previous study found that clinically relevant non-major bleeding occurred more frequently in TT carriers than rs1045642 (CC) carriers in a Caucasian population, but the ABCB1 rs1045642 polymorphism did not affect the pharmacokinetics of rivaroxaban in patients with non-valvular AF aged 80 years and older [20] . A retrospective analysis of Mongolian patients found that rs1128503 site variation was correlated with rivaroxaban blood concentration but not with bleeding events [21] .…”

Section: Discussionmentioning

confidence: 87%

An ADR pharmaceutical care for severe gastrointestinal bleeding of rivaroxaban in a patient with non-valvular atrial fibrillation based on TDM and genetic testing

Chen,

Huang,

Gao

et al. 2024

Preprint

View full text Add to dashboard Cite

Background Due to its predictable pharmacodynamics and pharmacokinetics, stable blood concentration, and relatively short half-life, rivaroxaban is widely used in the prevention and treatment of thrombosis. It nevertheless exhibits a certain level of inter-individual variability, and its safety concerns, including bleeding, are also becoming more noteworthy. Case presentation: This paper describes an elderly patient with nonvalvular atrial fibrillation that was complicated with coronary heart disease, who is a homozygous mutation carrier of the ABCB1 allele (rs1045642 C > T, rs1128503 C > T, rs2032582 G > T). He was developed severe gastrointestinal bleeding during administration of oral rivaroxaban combined with aspirin. We investigated the possible causes of the bleeding, and any potential correlation with the ABCB1 gene polymorphism, combined with antiplatelet drugs and anemia. Conclusion In the treatment of patients with atrial fibrillation, doctors should pay close attention to drug interactions with antiplatelet agents in high-risk groups and closely monitor various examination indexes, including hemoglobin. In this case, bleeding may have been associated with homozygous mutations in ABCB1, but more clinical data are needed to clarify the association between ABCB1 polymorphism and rivaroxaban pharmacokinetics and bleeding.

show abstract

Section: Discussionmentioning

confidence: 87%

An ADR pharmaceutical care for severe gastrointestinal bleeding of rivaroxaban in a patient with non-valvular atrial fibrillation based on TDM and genetic testing

Chen,

Huang,

Gao

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Inline with the findings regarding ADRs, Sychev et al's study revealed that rs1045642 is correlated with a decreased maximum concentration of rivaroxaban [ 26 ] although data from Nakagawa et al's study did not indicate significant results [ 24 ].…”

Section: Resultsmentioning

confidence: 97%

Pharmacogenetic Approach for the Prevention of Rivaroxaban’s ADRs: A Systematic Review and Meta-Analysis

Mardi,

Abbasi,

Shafiee

et al. 2023

Genetics Research

View full text Add to dashboard Cite

Introduction. Pharmacogenetics is a potential approach that can be applied to decline the burden of rivaroxaban’s ADRs. The current systematic review and meta-analysis aim to identify genetic variants correlated with rivaroxaban exposure and evaluate their importance. Methods. We systematically searched PubMed, Web of Science, and Scopus databases for all observational and interventional studies. The fixed effect method was used to pool the data when the Q-test’s p value was higher than 0.1. We used random models when the p value was less than 0.1. Results. Data from ten studies (4721 participants) were analyzed in the current review. Qualitative synthesis from included studies found that two variants of ABCB1 (rs1045642 and rs2032582) and one variant of APOB (rs13306198) are potential contributors to rivaroxaban concentrations. Both wild homozygotes (AA) and heterozygotes (AC) of rs1045642 have significantly lower rivaroxaban concentrations compared to mutated homozygotes (CC) (SMD = 0.516, 95% CI: 0.115 to 0.917; SMD = 0.772, 95% CI: 0.088 to 1.455, respectively). Nevertheless, pooling unadjusted odds ratios did not yield a statistically significant correlation between rivaroxaban ADRs and genetic mutations. Conclusion. This study revealed that being an AC or CC for rs1045642 is attributed to a considerably higher rivaroxaban level in participants using rivaroxaban. That is to say, rs1045642 is a remarkable predictor of rivaroxaban metabolism. We concluded that identifying rs1045642 before drug administration might decrease ADRs although further studies adjusted for potential confounders are strongly suggested.

show abstract

“…Likewise, a report that included 155 NVAF patients of Mongolian descent started on rivaroxaban, reported similar raw prevalence of genotypes at ABCB1 polymorphisms rs1128503, rs1045642 and rs4148738 in patients who experienced bleeding over the initial 7-10 days of treatment and in those who did not, but there were only 24 of the former, and the observational period was extremely short ( 42 ). In a cross-sectional study in 128 Russian NVAF patients older than 80 years of age with at least 7 days of treatment with rivaroxaban, 23 had a history of CRNMB ( 43 ). The authors report higher raw proportion of “bleeders” among rs1045642 variant homozygotes (12/41) vs. wild-type subjects (1/22), and among rs4148738 variant homozygotes (11/28) vs .…”

Section: Discussionmentioning

confidence: 99%

Common P-glycoprotein (ABCB1) polymorphisms do not seem to be associated with the risk of rivaroxaban-related bleeding events

Šimičević,

Trkulja,

Bulum

et al. 2024

Biochem. med. (Online)

View full text Add to dashboard Cite

show abstract

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

Cited by 10 publications

References 42 publications

An ADR pharmaceutical care for severe gastrointestinal bleeding of rivaroxaban in a patient with non-valvular atrial fibrillation based on TDM and genetic testing

An ADR pharmaceutical care for severe gastrointestinal bleeding of rivaroxaban in a patient with non-valvular atrial fibrillation based on TDM and genetic testing

Pharmacogenetic Approach for the Prevention of Rivaroxaban’s ADRs: A Systematic Review and Meta-Analysis

Common P-glycoprotein (ABCB1) polymorphisms do not seem to be associated with the risk of rivaroxaban-related bleeding events

Contact Info

Product

Resources

About