Dongxu Wang, Yang An, Xiaoyue Zhou, Huaru Chai, Jiani Huo, Chunrong Li, Minghui Du, Dapeng Dai, Chuanbao Li, Hao Chen
{"title":"服用直接作用口服抗凝剂的中国患者中所选择的药物遗传多态性与出血和血栓栓塞风险的相关性","authors":"Dongxu Wang, Yang An, Xiaoyue Zhou, Huaru Chai, Jiani Huo, Chunrong Li, Minghui Du, Dapeng Dai, Chuanbao Li, Hao Chen","doi":"10.1002/bcp.70078","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Relevance of selected pharmacogenetic polymorphisms to bleeding and thromboembolic risks in Chinese patients taking direct-acting oral anticoagulants.\",\"authors\":\"Dongxu Wang, Yang An, Xiaoyue Zhou, Huaru Chai, Jiani Huo, Chunrong Li, Minghui Du, Dapeng Dai, Chuanbao Li, Hao Chen\",\"doi\":\"10.1002/bcp.70078\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aims: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":9251,\"journal\":{\"name\":\"British journal of clinical pharmacology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2025-05-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"British journal of clinical pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/bcp.70078\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"British journal of clinical pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/bcp.70078","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Relevance of selected pharmacogenetic polymorphisms to bleeding and thromboembolic risks in Chinese patients taking direct-acting oral anticoagulants.
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.
期刊介绍:
Published on behalf of the British Pharmacological Society, the British Journal of Clinical Pharmacology features papers and reports on all aspects of drug action in humans: review articles, mini review articles, original papers, commentaries, editorials and letters. The Journal enjoys a wide readership, bridging the gap between the medical profession, clinical research and the pharmaceutical industry. It also publishes research on new methods, new drugs and new approaches to treatment. The Journal is recognised as one of the leading publications in its field. It is online only, publishes open access research through its OnlineOpen programme and is published monthly.