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首页> 外文期刊>Ukrainian Biochemical Journal >Warfarin therapy in patients with coronary heart disease and atrial fibrillation: drug interactions and genetic sensitivity to warfarin
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Warfarin therapy in patients with coronary heart disease and atrial fibrillation: drug interactions and genetic sensitivity to warfarin

机译：冠心病患者的华法林治疗和心房颤动：药物相互作用和对华法林的遗传敏感性

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In this research work we examined the effect of various factors on the efficacy and safety of warfarin pharmacotherapy. Particular emphasis was placed on drug interaction in the standardized treatment of patients with coronary heart disease and atrial fibrillation. Since the administration of such drugs as digoxin and statins with warfarin leads to an increase in the blood level of all three drugs (they interact at the level of P-glycoprotein) and warfarin has a narrow therapeutic window, the risk of hemorrhagic complications is increased. For the first time in patients of the Podillya region of Ukraine, the genetic polymorphism of cytochrome CYP2C9 was determined, which is associated with the slow withdrawal of anticoagulant from the bloodstream and the possible risk of bleeding. For safe pharmacotherapy, patients were given significantly different doses of warfarin in all comparison groups, according to the International Normalized Ratiо (INR). For example, in the group with a CYP2C9 mutation present, the dose was 3.08 ± 0.25 mg versus 4.15 ± 0.22 mg in the non-mutation group ( P = 0.008). In addition, in patients with genetic polymorphism of detoxification enzymes, significantly more bleeding events (light or clinically significant; critical organ bleeding) were observed, but among these patients bleeding occurred at an INR of 2.6 (despite the recommendations of the European Society of Cardiology, that the INR can be maintained within 2.0-3.0). Therefore, patients with CYP2C9 mutations require a personalized approach and control of the INR in a safer range (2.0 to 2.5) and consideration of drug interactions.
机译：在这项研究中，我们研究了各种因素对华法林药物治疗的疗效和安全的影响。特别强调在冠心病和心房颤动的标准治疗中的药物相互作用。由于这些药物作为Digoxin和患有华法林的他汀类药物的给药导致所有三种药物的血液水平增加（它们在P-糖蛋白的水平上相互作用）和Warfarin具有狭窄的治疗窗口，出血性并发症的风险增加。在乌克兰的Podillya地区的患者中，确定了细胞色素CYP2C9的遗传多态性，其与血液中的抗凝血剂缓慢戒断和出血的可能风险有关。根据国际标准化RATI®（INR），对于安全的药物治疗，患者在所有比较组中均为患者在所有比较组中具有显着不同的华法林。例如，在具有CYP2C9突变的组中，剂量为3.08±0.25mg，非突变组中的4.15±0.22mg（p = 0.008）。此外，在解毒酶的遗传多态性患者中，观察到更高的出血事件（光或临床显着;关键器官出血），但在这些患者中出血发生在2.6的INR（尽管欧洲心脏病学会的建议） ，INR可以保持在2.0-3.0中）。因此，CYP2C9突变的患者需要个性化方法和控制更安全范围（2.0至2.5）的INR，并考虑药物相互作用。

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