Key result
Genetic polymorphisms in CES1 and ABCB1 influence the pharmacokinetics of dabigatran, rivaroxaban, and apixaban, though current evidence is insufficient to recommend routine pharmacogenetic testing.
Why the study?
DOACs show high inter-individual variability in pharmacodynamics and pharmacokinetics that could result from genetic polymorphisms, prompting a review of studies associating single nucleotide polymorphisms with systemic exposure variation.
Do single nucleotide polymorphisms affect the systemic exposure variation of direct oral anticoagulants?
Systematic Review
Do single nucleotide polymorphisms affect the systemic exposure variation of direct oral anticoagulants?
Genetic polymorphisms in CES1 and ABCB1 genes are associated with systemic exposure variations of dabigatran, rivaroxaban, and apixaban, suggesting a potential role for pharmacogenetic testing to optimize DOAC therapy.
Dabigatran, rivaroxaban, apixaban, edoxaban, and betrixaban are direct oral anticoagulants (DOACs). Their inter-individual variability in pharmacodynamics and pharmacokinetics (transport and metabolism) is high, and could result from genetic polymorphisms. As recommended by the French Network of Pharmacogenetics (RNPGx), the management of some treatments in cardiovascular diseases (as antiplatelet agents, oral vitamin K antagonists, and statins) can rely on genetic testing in order to improve healthcare by reducing therapeutic resistance or toxicity. This paper is a review of association studies between single nucleotide polymorphisms (SNPs) and systemic exposure variation of DOACs. Most of the results presented here have a lot to do with some SNPs of CES1 (rs2244613, rs8192935, and rs71647871) and ABCB1 (rs1128503, rs2032582, rs1045642, and rs4148738) genes, and dabigatran, rivaroxaban, and apixaban. Regarding edoxaban and betrixaban, as well as SNPs in the CYP3A4 and CYP3A5 genes, literature is scarce, and further studies are needed.
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Raymond et al. (2021) conducted a systematic review in Cardiovascular diseases requiring direct oral anticoagulants (DOACs). Genetic polymorphisms (CES1, ABCB1, CYP3A4, CYP3A5) vs. Wild-type genotypes was evaluated on Systemic exposure variation of DOACs and risk of hemorrhage or thromboembolic events. Genetic polymorphisms in CES1 and ABCB1 influence the pharmacokinetics of dabigatran, rivaroxaban, and apixaban, though current evidence is insufficient to recommend routine pharmacogenetic testing.
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