Pharmacogenetics of Direct Oral Anticoagulants: A Systematic Review

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.

Automated summary

DOACs, such as dabigatran, rivaroxaban, apixaban, edoxaban, and betrixaban, exhibit high inter-individual variability in pharmacodynamics and pharmacokinetics, likely due to genetic polymorphisms. Genetic testing can improve healthcare in cardiovascular diseases by reducing therapeutic resistance or toxicity, especially in antiplatelet agents, oral vitamin K antagonists, and statins. Studies on the association between single nucleotide polymorphisms (SNPs) and systemic exposure variation of DOACs mainly focus on certain SNPs in CES1 and ABCB1 genes related to dabigatran, rivaroxaban, and apixaban, while research on edoxaban, betrixaban, and SNPs in CYP3A4 and CYP3A5 genes is limited and requires further investigation.