Relevance of selected pharmacogenetic polymorphisms to bleeding and thromboembolic risks in Chinese patients taking direct-acting oral anticoagulants.

Abstract

Aims: Gene polymorphisms play a critical role in the variability of plasma concentrations of direct-acting oral anticoagulants (DOACs). In this study, we aimed to investigate the effects of genetic variants on the clinical outcomes of Chinese patients treated with DOACs.

Methods: The retrospective study recruited 720 patients with nonvalvular atrial fibrillation who were receiving dabigatran, rivaroxaban or edoxaban. Cox regression models were employed to compare the clinical outcomes between carriers and noncarriers of the key single nucleotide polymorphisms.

Results: Results revealed that the CES1 rs2244613 C allele significantly reduced bleeding events in patients treated with dabigatran (adjusted hazard ratio 0.33, 95% confidence interval 0.13-0.85, P = .021). The carriage of ABCB1 rs1045642 T allele was associated with a lower risk of thromboembolism in rivaroxaban users (adjusted hazard ratio 0.19, 95% confidence interval 0.07-0.57, P = .003). Additionally, a trend toward statistical significance (P = .052) was observed between the SLCO1B1 rs4149056 C allele and bleeding risk among the edoxaban users.

Conclusions: Our study showed that the CES1 rs2244613 and ABCB1 rs1045642 alleles were associated with outcome events in Chinese patients taking dabigatran and rivaroxaban, respectively. The findings could help predict clinical outcomes and develop personalized anticoagulation treatment strategies for Chinese patients taking DOACs.