基因分型指导非瓣膜性房颤患者华法林抗凝治疗的研究

Genotype-guided warfarin anticoagulant therapy in patients with non-valvular atrial fibrillation

目的:评价基因分型指导非瓣膜性房颤(NVAF)患者华法林抗凝治疗的有效性及安全性,探讨基因检测技术在华法林个体化治疗中的意义。方法:纳入符合条件的CHA2DS2-VASc≥2分(即卒中高危者)、无用药禁忌且初次使用华法林抗凝的NVAF患者,随机分为常规治疗组和个体化治疗组。常规治疗组给予华法林3 mg·d^(-1)起始治疗;个体化治疗组检测CYP2C9*2、CYP2C9*3和VKORC1(G-1639A)基因多态性,依据国际华法林遗传药理学联盟的权威公式计算的初始剂量进行治疗;两组常规监测INR,使INR维持在2.0~3.0之间;随访3个月,比较两组INR达标所需时间、主要出血/血栓栓塞事件的差异。结果:两组基线特征比较差异无统计学意义(P>0.05);个体化治疗组INR达标所需时间短(P<0.05);常规治疗组有1例发生脑卒中,6例发生轻微出血(牙龈/鼻腔出血、皮肤淤斑和血尿),两组比较差异有统计学意义(P<0.05)。结论:基于基因多态性的华法林初始剂量预测模型对实现华法林个体化治疗具有一定指导意义,INR达标时间更早且临床疗效更高。

OBJECTIVE To evaluate efficacy and safety of genotype-guided warfarin therapy in patients with non-valvular atrial fibrillation（NVAF）,and further explore its clinical significance.METHODS Qualified patients with NVAF（CHA2DS2-VASc≥2）were enrolled and randomly divided into routine treatment（RT）group and individualized treatment（IT）group.Patients in RTG group received warfarin at the initial dose of 3 mg·d^-1.For patients in IT group,CYP2C9＊2,CYP2C9＊3 and VKORC1（g^-1639A）were detected,and initial dose was calculated by using typical algorithm issued by International Warfarin Pharmacogenetics Consortium.INR was monitored routinely for both groups and maintained in range of 2.0～3.0.All patients were followed up for 3 months to compare the differences in time to target INR,and major events including hemorrhage/embolism.RESULTS No significant difference was observed in baseline characteristics（P〈0.05）.IT group had a shorter time to target INR（P〈0.05）.RT group had1 case of cerebral stroke and6 cases of mild hemorrhage,and showed statistically significant difference compared to IT group（P〈0.05）.CONCLUSION Genotype-guided warfarin therapy based on gene polymorphism has certain guiding significance to individualized warfarin therapy,short time to target INR and superior clinical efficacy.