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    肾功能对心房颤动患者华法林抗凝过度的影响

    Effect of Renal Function for Excessive Anticoagulation with Warfarin in Patients with Atrial Fibrillation

      摘要
    • 摘要:
      目的  探讨估算肾小球滤过率(estimateol glomerular filtration rate，eGFR)水平与接受华法林治疗的心房颤动患者抗凝过度的关系，评价其对接受华法林治疗的心房颤动患者抗凝过度的预测价值。
      方法  回顾性纳入接受华法林治疗的心房颤动患者838例，均在用药7 d后的次日清晨检测国际标准化比值(international normalized ratio，INR)，按照用药7 d后INR是否>3.0，将患者分为抗凝过度组(173例)和非抗凝过度组(665例)。分析2组患者的一般临床资料，使用受试者工作特征(receiver operating characteristic，ROC)曲线评价用药eGFR水平预测接受华法林治疗的心房颤动患者抗凝过度的价值，采用Logistic回归方程分析接受华法林治疗的心房颤动患者抗凝过度的相关因素。
      结果  抗凝过度组患者年龄、联合用药数量、血清天冬氨酸氨基转移酶(aspartate transaminase，AST)水平均高于非抗凝过度组(P<0.05)；转氨酶异常、联用胺碘酮比例均高于非抗凝过度组(P<0.05)。抗凝过度组患者体质量、血清白蛋白、eGFR水平均低于非抗凝过度组(P<0.05)，合并糖尿病比例低于非抗凝过度组(P<0.05)。ROC曲线显示eGFR预测华法林抗凝过度的AUC为0.651(95% CI 0.605~0.696， P<0.001)，灵敏度57.80%，特异度65.86%；此时预测抗凝过度的最佳界值eGFR≤70 mL·min‒1·(1.73 m2)‒1。多因素Logistic回归显示，eGFR≤70 mL·min‒1(OR=2.445，95%CI 1.709~3.498，P<0.001)，转氨酶异常(OR=1.693，95%CI 1.148~2.496，P=0.008)，华法林初始剂量(OR=1.596，95%CI 1.065~2.394，P=0.024)，联用胺碘酮(OR=1.626，95%CI 1.093~2.419，P=0.016)是华法林稳态抗凝强度时发生抗凝过度的独立危险因素，而糖尿病(OR=0.333，95%CI 0.171~0.694，P=0.003)是华法林稳态抗凝强度时发生抗凝过度的保护因素。
      结论  eGFR水平与心房颤动患者华法林抗凝过度密切相关，对华法林抗凝过度有一定的预测价值，对于eGFR≤70 mL·min‒1·(1.73 m2)‒1、转氨酶异常、华法林初始剂量高、联用胺碘酮的患者应加强INR监测，以降低抗凝过度风险。

       

      Abstract:
      OBJECTIVE To explore the relationship between the level of estimated glomerular filtration rate(eGFR) and excessive anticoagulation in atrial fibrillation patients treated with warfarin, and to evaluate its predictive value for excessive anticoagulation in atrial fibrillation patients treated with warfarin.
      METHODS A total of 838 patients with atrial fibrillation who received warfarin treatment were retrospectively included. International normalized ratio(INR) was measured on the morning of the day following the 7th day of medication for all patients. They were divided into the over-anticoagulation group(173 cases) and the non-over-anticoagulation group(665 cases) based on whether INR was > 3.0 after 7 days of medication. General clinical data of the two groups were analyzed. The value of eGFR level in predicting over-anticoagulation in atrial fibrillation patients receiving warfarin treatment was evaluated using the receiver operating characteristic(ROC) curve. Logistic regression equation was used to analyze the related factors of over-anticoagulation in atrial fibrillation patients receiving warfarin treatment.
      RESULTS Patients in the over-anticoagulation group had higher age, number of combined medications, and aspartate transaminase(AST) levels than those in the non-over-anticoagulation group(P<0.05); the proportion of abnormal transaminase and combined use of amiodarone was also higher in the over-anticoagulation group(P<0.05). The body weight, albumin, and eGFR levels of patients in the over-anticoagulation group were lower than those in the non-over-anticoagulation group(P<0.05), and the proportion of diabetes was lower in the over-anticoagulation group(P<0.05). The ROC curve showed that the AUC of eGFR for predicting over-anticoagulation with warfarin was 0.651(95%CI: 0.605−0.696, P<0.001), with a sensitivity of 57.80% and a specificity of 65.86%; at this time, the optimal cut-off value of eGFR for predicting over-anticoagulation was ≤ 70 mL·min‒1·(1.73 m2)‒1. Multivariate Logistic regression showed that eGFR ≤ 70 mL·min‒1·(1.73 m2)‒1(OR=2.445, 95%CI 1.709−3.498, P<0.001), abnormal transaminase(OR=1.693, 95%CI 1.148−2.496, P=0.008), initial dose of warfarin(OR=1.596, 95%CI 1.065−2.394, P=0.024), and combined use of amiodarone(OR=1.626, 95%CI 1.093−2.419, P=0.016) were independent risk factors for over-anticoagulation at the steady state of warfarin anticoagulation intensity, while diabetes(OR=0.333, 95%CI 0.171−0.694, P=0.003) was a protective factor for over-anticoagulation at the steady state of warfarin anticoagulation intensity.
      CONCLUSION The eGFR level is closely related to the occurrence of excessive anticoagulation with warfarin in patients with atrial fibrillation and has certain predictive value for it. INR monitoring should be intensified in patients with eGFR≤70 mL·min‒1·(1.73 m2)‒1, abnormal transaminases, high initial dose of warfarin, and concomitant amiodarone to reduce the risk of excessive anticoagulation.

       

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