Thrombosis Research Unit, Aalborg University, Aalborg, Denmark.
Department of Cardiology, Aalborg AF study group, Aalborg University Hospital, Aalborg, Denmark.
Thromb Res. 2014 Mar;133(3):375-9. doi: 10.1016/j.thromres.2013.12.042. Epub 2014 Jan 7.
Warfarin is the most widely prescribed vitamin K antagonist and in the United States and Europe more than 10 million people are currently in long-term oral anticoagulant treatment. This study aims to retrospectively validate a dynamic statistical model providing dosage suggestions to patients in warfarin treatment.
The model was validated on a cohort of 553 patients with a mean TTR of 83%. Patients in the cohort were self-monitoring and managed by a highly specialised anticoagulation clinic. The predictive model essentially consists of three parts handling INR history, warfarin dosage and biological noise, which allows for prediction of future INR values and optimal warfarin dose to stay on INR target. Further, the model is based on parameters initially being set to population values and gradually individualised during monitoring of patients.
Time in therapeutic range was used as surrogate quality measure of the treatment, and model-suggested dosage of warfarin was used to assess the accuracy of the model performance.
The accuracy of the model predictions measured as median absolute error was 0.53 mg/day (interquartile range from 0.25 to 1.0). The model performance was evaluated by the difference between observed and predicted warfarin intake in the preceding week of an INR measurement. In more than 70% of the cases where INR measurements were outside the therapeutic range, the model suggested a more reasonable dose than the observed intake.
Applying the proposed dosing algorithm can potentially further increase the time in INR target range beyond 83%.
华法林是最广泛应用的维生素 K 拮抗剂，目前美国和欧洲有超过 1000 万人正在接受长期口服抗凝治疗。本研究旨在回顾性验证一种为华法林治疗患者提供剂量建议的动态统计模型。
该模型在一个平均 TTR 为 83%的 553 名患者队列中进行了验证。该队列中的患者进行自我监测，并由一个高度专业化的抗凝诊所管理。该预测模型主要由三个部分组成，分别处理 INR 历史、华法林剂量和生物学噪声，从而可以预测未来的 INR 值和保持 INR 目标的最佳华法林剂量。此外，该模型基于初始设定为群体值的参数，并在监测患者期间逐渐个体化。
治疗时间范围（TTR）被用作治疗的替代质量指标，华法林的模型建议剂量用于评估模型性能的准确性。
模型预测的准确性以中位数绝对误差衡量为 0.53 毫克/天（四分位距为 0.25 至 1.0）。通过观察到的 INR 测量前一周的华法林摄入量与预测值之间的差异来评估模型的性能。在超过 70%的 INR 测量值超出治疗范围的情况下，模型建议的剂量比观察到的摄入量更合理。
应用所提出的剂量算法有可能进一步将 INR 目标范围内的时间延长到 83%以上。
