新疆某地区老年心房颤动患者华法林稳定剂量预测模型的验证与评价

Validation and Evaluation of Warfarin Stable Dose Prediction Algorithm in the Elderly with Atrial Fibrillation in An Area of Xinjiang

目的:比较目前常用的华法林剂量预测模型在新疆某地区≥60岁人群中的预测准确性。方法:纳入2018年10月至2020年10月新疆维吾尔自治区人民医院因心房颤动服用华法林并已达标的≥60岁老年患者,检测重要的华法林药物代谢基因CYP2C9及VKORC1,收集患者的基本信息,采用预测百分比和绝对误差均值法评价各模型预测的准确性。结果:共入组61例患者,其中CYP2C9*1/*1、CYP2C9*1/*3和CYP2C9*3/*3基因型患者分别占88.52%(54例)、8.20%(5例)和3.28%(2例),VKORC1-1639AA、AG和GG基因型患者分别占68.85%(42例)、22.95%(14例)和8.20%(5例)。CYP2C9*1/*1合并VKORC1-1639GG基因型患者的华法林达标剂量最高,为(6.51±0.96)mg/d;CYP2C9*1/*1合并VKORC1-1639AG基因型患者的华法林达标剂量次之,为(4.26±1.14)mg/d;CYP2C9*1/*3合并VKORC1-1639GG基因型患者的华法林达标剂量为(3.28±1.45)mg/d,稍高于CYP2C9*1/*1合并VKORC1-1639AA基因型患者[(3.13±0.83)mg/d],两者均高于CYP2C9*1/*3合并VKORC1-1639AA基因型患者[(2.07±1.32)mg/d];CYP2C9*1/*3合并VKORC1-1639AG、CYP2C9*3/*3合并VKORC1-1639AA和CYP2C9*3/*3合并VKORC1-1639AG基因型患者的华法林达标剂量均<1 mg/d。预测效果较好的模型包括国际华法林药物基因学联盟(IWPC)模型(理想预测剂量35例,占57.38%)、《药物代谢酶和药物作用靶点基因检测技术指南(试行)》(2015年)(简称"指南模型")(理想预测剂量40例,占65.57%),其绝对误差均值分别为0.70 mg/d(95%CI=0.56~0.84)、0.87 mg/d(95%CI=0.56~1.89)。结论:基于CYP2C9及VKORC1基因多态性对新疆某地区心房颤动患者的华法林稳定剂量存在影响,IWPC模型和指南模型更适用于新疆某地区≥60岁人群。

OBJECTIVE:To compare the predictive accuracy of currently used warfarin dose prediction algorithm in the elderly aged≥60 years in an area of Xinjiang.METHODS:The elderly aged≥60 years who had reached the standard of warfarin administration for atrial fibrillation in People’s Hospital of Xinjiang Uygur Autonomous Region from Oct.2018 to Oct.2020 were enrolled to detect the important warfarin drug metabolism genes CYP2 C9 and VKORC1.Basic information of patients was collected,and the accuracy of each model was evaluated by percentage prediction and mean absolute error.RESULTS:A total of 61 patients were enrolled,among which CYP2 C9*1/*1,CYP2 C9*1/*3 and CYP2 C9*3/*3 genotype patients accounted for 88.52%(54 cases),8.20%(5 cases)and 3.28%(2 cases),respectively.VKORC1-1639 AA,AG and GG genotype patients accounted for 68.85%(42 cases),22.95%(14 cases)and 8.20%(5 cases),respectively.Patients with CYP2 C9*1/*1 combined with VKORC1-1639 GG genotype had the highest target dose of warfarin at(6.51±0.96)mg/d;followed by patients with CYP2 C9*1/*1 combined with VKORC1-1639 AG genotype at target dose of warfarin of(4.26±1.14)mg/d.The target dose of warfarin of CYP2 C9*1/*3 combined with VKORC1-1639 GG genotype was(3.28±1.45)mg/d,slightly higher than(3.13±0.83)mg/d of CYP2 C9*1/*1 combined with VKORC1-1639 AA genotype,both were higher than(2.07±1.32)mg/d of CYP2 C9*1/*3 combined with VKORC1-1639 AA genotype.The target doses of warfarin in patients with CYP2 C9*1/*3 combined with VKORC1-1639 AG,CYP2 C9*3/*3 combined with VKORC1-1639 AA and CYP2 C9*3/*3 combined with VKORC1-1639 AG genotype were<1 mg/d.The models with better prediction results included the International Warfarin Pharmacogenetics Consortium(IWPC)model(ideal predicted dose in 35 cases,57.38%),Technical Guidance for Genetic Detection of Drug Metabolism Enzymes and Drug Action Targets(Trial)(2015)(referred to as“guideline model”)(ideal predicted dose in 40 cases,65.57%),the mean absolute errors were 0.70 mg/d(95%CI=0.56-0.84)and 0.87 mg/d(95%CI=0.56-1.89),respectively.CONCLUSIONS:Based on the influence of CYP2 C9 and VKORC1 gene polymorphisms on the stable dose of warfarin in patients with atrial fibrillation in this area of Xinjiang,the IWPC model and the guideline model are more suitable for people aged≥60 years in this area of Xinjiang.