心房颤动(AF)占所有心律失常的40%,并且与中风和全身性血栓栓塞并发症的高风险相关。达比加群,利伐沙班,阿哌沙班,和edoxaban是直接口服抗凝药(DOAC),已被证明可预防非瓣膜性房颤患者的卒中。这篇综述总结了药代动力学,药效学,和DOAC的药物相互作用,以及这些药物的药物遗传学研究的新数据。这篇综述旨在分析有关DOAC代谢涉及的基因多态性的科学文献。我们搜索了PubMed,科克伦,谷歌学者,和CyberLeninka(俄语版本)数据库的关键字:\'dabigatran\',\'apixaban\',\'利伐沙班\',\'edoxaban\',\'基因多态性\',\'药物遗传学\',\'ABCB1\',\'CES1\',\'SULT1A\',\'ABCG2\',和\'CYP3A4\'。本综述引用的文章包括(1)全文文章;(2)采用荟萃分析的研究设计,在服用DOAC的患者中进行的观察性研究;和(3)DOAC的单核苷酸多态性和动力学参数(血浆浓度)的数据,或特定的临床结果,在过去10年中以英语和俄语出版。患者的年龄范围为18至75岁。在114件审查的作品中,有24人符合条件。根据现有的药物基因组数据,影响DOAC的多态性是不同的。这可能有助于开发优化DOAC药物治疗的单独方法,以降低出血性并发症的风险。然而,需要进行大规模人群研究,根据基因分型确定新型口服抗凝剂的剂量.由于缺乏大规模研究,有关遗传效应的信息有限。揭示DOAC敏感性的遗传基础的机制有助于开发基于患者特异性遗传变异的个性化治疗,并提高DOAC在普通人群中的疗效和安全性。
基因多态性是口服维生素K非依赖性抗凝剂治疗的非瓣膜性心房颤动患者出血性并发症的原因。心房颤动(AF)占所有心律失常的40%,并与中风和全身性血栓栓塞并发症的高风险相关。达比加群,利伐沙班,阿哌沙班,和edoxaban是直接口服抗凝药(DOAC),已被证明可预防非瓣膜性房颤患者的卒中。这篇综述总结了药代动力学,药效学,和DOAC的药物相互作用,以及这些药物的药物遗传学研究的新数据。
Atrial fibrillation (AF) accounts for 40% of all cardiac arrhythmias and is associated with a high risk of stroke and systemic thromboembolic complications. Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that have been proven to prevent stroke in patients with non-valvular AF. This review summarizes the pharmacokinetics, pharmacodynamics, and drug interactions of DOACs, as well as new data from pharmacogenetic studies of these drugs. This review is aimed at analyzing the scientific literature on the gene polymorphisms involved in the metabolism of DOACs. We searched PubMed, Cochrane, Google Scholar, and CyberLeninka (Russian version) databases with keywords: \'dabigatran\', \'apixaban\', \'rivaroxaban\', \'edoxaban\', \'gene polymorphism\', \'pharmacogenetics\', \'ABCB1\', \'CES1\', \'SULT1A\', \'
ABCG2\', and \'CYP3A4\'. The articles referred for this review include (1) full-text articles; (2) study design with meta-analysis, an observational study in patients taking DOAC; and (3) data on the single-nucleotide polymorphisms and kinetic parameters of DOACs (plasma concentration), or a particular clinical outcome, published in English and Russian languages during the last 10 years. The ages of the patients ranged from 18 to 75 years. Out of 114 reviewed works, 24 were found eligible. As per the available pharmacogenomic data, polymorphisms affecting DOACs are different. This may aid in developing individual approaches to optimize DOAC pharmacotherapy to reduce the risk of hemorrhagic complications. However, large-scale population studies are required to determine the dosage of the new oral anticoagulants based on genotyping. Information on the genetic effects is limited owing to the lack of large-scale studies. Uncovering the mechanisms of the genetic basis of sensitivity to DOACs helps in developing personalized therapy based on patient-specific genetic variants and improves the efficacy and safety of DOACs in the general population.
Gene polymorphism as a cause of hemorrhagic complications in patients with non-valvular atrial fibrillation treated with oral vitamin K-independent anticoagulantsAtrial fibrillation (AF) accounts for 40% of all cardiac arrhythmias and is associated with a high risk of stroke and systemic thromboembolic complications. Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that have been proven to prevent stroke in patients with non-valvular AF. This review summarizes the pharmacokinetics, pharmacodynamics, and drug interactions of DOACs, as well as new data from pharmacogenetic studies of these drugs.