非瓣膜性房颤患者达比加群血药浓度监测及对出血风险预测效果评价研究

目的 探讨非瓣膜性房颤患者达比加群血药浓度的影响因素及临床意义,评价血药浓度对达比加群酯出血事件的预测能力。方法 分析143例达比加群稳态血药谷浓度监测结果,采用t检验分析年龄、性别、肌酐清除率(Ccr)、合并用药对达比加群血药浓度的影响;运用受试者工作特征曲线(ROC)分析评估达比加群血药浓度对出血事件的预测能力。结果 143例患者达比加群血药浓度受年龄、性别、Ccr影响(P＜0.05),与活化部分凝血活酶时间(APTT)呈正相关;25例患者发生小出血,APTT、Ccr和血药浓度与出血事件有相关性(P＜0.05),血药浓度预测出血事件的ROC曲线下面积为0.909(P<0.001),曲线中Youden指数最大(0.713)时对应的最佳临界值为154.35 ng·mL^-1,灵敏度和特异度分别为84%和87%,优于Ccr。结论 非瓣膜性房颤患者达比加群血药浓度临床个体差异较大,且血药浓度对出血事件预测灵敏度和特异性高,可为临床个体化用药和安全用药提供指导。

TDM Monitoring,Evaluation for Predicting the Hemorrhage Risk of Dabigatran Concentration in Non-Valvular Atrial Fibrillation

OBJECTIVE To explore the influencing factors and clinical significance of dabigatran concentration in patients with non-valvular atrial fibrillation, and to evaluate the predictive ability of dabigatran concentration on hemorrhage events. METHODS Analysis was performed on results of 143 cases with steady-state dabigatran concentration monitoring, T-test was used to analyze the effects of age, gender, creatinine clearance rate(Ccr) and combined drugs on the blood concentration of dabigatran. The ability of dabigatran concentration predicting hemorrhage risk was assessed by ROC curve. RESULTS In 143 patients, age, sex and creatinine clearance had significant effects on the blood concentration of dabigatran(P＜0.05), which was positively correlated with APTT. Small hemorrhage events occurred in 25 patients. APTT, Ccr and blood drug concentration were correlated with hemorrhage events (P<0.05). The dabigatran concentration demonstrated good discrimination performance for prediction in hemorrhage events at the best cut-off value of 154.35 ng·mL^-1, the sensitivity and specificity to predict hemorrhage events were 84% and 87%, respectively. The Youden index for the cut-off value was the highest(0.713), which was better than Ccr. CONCLUSION The concentration of dabigatran in patients with non-valvular atrial fibrillation has great clinical individual differences, and has high sensitivity and specificity in predicting hemorrhage events,it can provide guidance for clinical individualized and safe medication.