影响中国汉族≥75岁老年口服华法林病人IWPC预测模型准确性的相关因素

Relevant factors influencing the accuracy of IWPC prediction model in Chinese Han elderly patients with oral warfarin

目的探讨影响≥75岁老年病人国际华法林药物基因组协会(IWPC)预测模型准确性的相关因素,为≥75岁病人更合理地应用华法林提供参考。方法收集≥75岁口服华法林抗凝治疗的老年病人的临床资料,根据预测剂量与实际剂量间的差异率分为差异轻微组、差异一般组和差异显著组,比较各组性别、年龄、BMI、血压、心率、合并疾病及合并用药等临床指标差异,并分析各指标与剂量差异率的相关性。结果73例病人分为差异轻微组42例,差异一般组21例,差异显著组10例。3组病人性别、年龄、肝功能等指标及各基因型分布差异无统计学意义(P>0.05)。差异轻微组心力衰竭(心衰)病史及应用利尿剂比例明显低于差异显著组,血清肌酐明显低于差异一般组及差异显著组,估算的肾小球率过滤(eGFR)明显高于差异一般组及差异显著组,差异有统计学意义(均P<0.05)。差异轻微组华法林实际剂量明显高于差异显著组(P<0.05)。有序多元Logistic回归分析显示,心衰病史及是否应用利尿剂对病人剂量差异率无显著影响(P>0.05)。将eGFR按四分位数分为低水平[<59.5 mL/(min·1.73m^2)]、中低水平[59.5~76.3 mL/(min·1.73m^2)]、中高水平[76.4~96.5 mL/(min·1.73m^2)]、高水平[>96.5 mL/(min·1.73m^2)]4个等级,eGFR低水平病人引起华法林实际与预测剂量间明显差异的OR值是eGFR高水平病人的4.455倍;eGFR中低水平病人引起华法林实际与预测剂量间明显差异的OR值是eGFR高水平病人的5.135倍。结论中国汉族≥75岁病人华法林平均实际稳定剂量<2.5 mg/d;实际剂量越低,与IWPC模型公式预测剂量差异越大;eGFR与剂量差异大小有显著相关性。

Objective To explore the related factors that affect the accuracy of international warfarin phamacogenetics consortium(IWPC)prediction model in the patients aged≥75 years old receiving warfarin,and to provide a reference for reasonable usage of warfarin.Methods The clinical data of the patients aged≥75 years old receiving warfarin were collected.According to the difference rate between the predicted dose and the actual dose,the patients were divided into mild difference group(42 cases),moderate difference group(21 cases),significant difference group(10 cases).The clinical indicators of each group,including gender,age,body mass index,blood pressure,heart rate,comorbidities and concomitant medication were compared,and the influencing factors were analyzed.Results There were no significant differences in sex,age,liver function index and genotype distribution among the three groups(P>0.05).The history of heart failure and the proportion of diuretics used in the mild difference group were significantly lower than those in the significant difference group,and the serum creatinine of mild difference group was significantly lower and the estimated glomerular filtration rate(eGFR)was significantly higher than that in the moderate difference group and the significant difference group(P<0.05).History of heart failure and diuretics showed no significant effects on the dosage of warfarin(P>0.05).According to the quartile,eGFR was divided into low level[<59.5 mL/(min·1.73m^2)],middle-low level[59.5~76.3 mL/(min·1.73m^2)],middle-high level[76.4~96.5 mL/(min·1.73m^2)]and high level[>96.5 mL/(min·1.73m^2)]group.The difference between the actual and predicted dose of warfarin caused by the low level of eGFR was 4.455 times of that of the high level of eGFR;The difference between the actual and predicted dose of warfarin caused by the middle-low level of eGFR was 5.135 times higher than that of the high level of eGFR.Conclusions The average actual stable dose of warfarin in the patients aged≥75 years old of Han Chinese is less than 2.5 mg/d,the lower of the actual dose,the greater of the difference with the predicted dose by IWPC model formula,and there is a significant correlation between eGFR and dose difference.