药理遗传学的方法指导心房颤动患者华法林使用剂量研究

Dose study on atrial fibrillation patients' warfarin use based on pharmacogenetics

目的研究药理遗传学的方法指导华法林使用剂量是否优于根据临床指标确定的华法林剂量用药方法。方法选取来自门诊或病房需要使用华法林抗凝心房颤动的患者220例,将其分为两组,一组按照药理遗传学方法确定的华法林剂量用药,采取聚合酶链反应-限制性内切核酸酶片段长度的多态性(PCR-RFLP)对患者进行CYP2C9和VKORC1基因型分析,根据计算模型确定的华法林剂量用药,并进行调整。另一组根据临床指标确定的华法林剂量用药。观察患者达标稳定时间、药物调整的次数、终点剂量与初始剂量的绝对差值、抗凝过量的比例,并观察随访过程中出血事件的严重程度和发生率。随访时间约半年。结果药理遗传学方法指导的华法林使用剂量与根据临床指标确定的华法林剂量用药方法相比,达标稳定时间、药物调整的次数、终点剂量与初始剂量的绝对差值、抗凝过量的比例(1.8%:16.4%)、严重出血事件发生率均体现出优势,差异具有统计学意义(P<0.05)。结论药理遗传学方法指导的华法林使用剂量比根据临床指标确定的华法林剂量用药方法使用的剂量更加精确,剂量调整小而少,而且严重出血发生率低,对患者更安全,值得推广应用。

Objective To compare the strengths of warfarin based on pharmacogenetics or defined by clinical indicators. Methods Either from outpatient or inpatient department, 220 patients who needed anticoagulative treatment by warfarin were recruited. These cases were divided into two groups. Warfarin use method of one group was determined by pharmacogenetics, specifically, CYP2C9 and VKORCI genotyping were carried out to ascertain and adjust use dosage by Polymerase chain reaction-restriction nuelease fragment length polymorphism （PCR-RFLP）. As for the other group, therapeutic regimen was defined by the stable and qualifying time, the frequency of drug adjustment, absolute difference between initial and eventual dose and the proportion of anticoagulant overdose. Additionally, the severity and incidence of hemorrhagic events were closely observed during half year＇s following up. Results Compared with traditional warfarin use regimen defined by clinical indicators, the results obtained by pharmacogenetics, including the stable and qualifying time, the frequency of drug adjustment, absolute difference between initial and eventual dose, the proportion of anticoagulant overdose （1.8% compared to 16.4%）, and the incidence of severe hemorrhagic events were unanimously better and statistically difference （P〈0.05）. Conclusion In terms of safety, dose accuracy, the frequency and scale of drug adjustment and the incidence of severe hemorrhagic events, warfarin use method determined by pharmacogenetics is superior to that defined by clinical indicators. Accordingly, it is worth promotion and application.