Background Warfarin remains widely used and a key comparator in studies of other direct oral anticoagulants. As longer-than-needed warfarin prescriptions are often provided to allow for dosing adjustments according to international normalized ratios (INRs), the common practice of using a short allowable gap between dispensings to define warfarin discontinuation may lead to substantial misclassification of warfarin exposure. We aimed to quantify such misclassification and determine the optimal algorithm to define warfarin discontinuation. Methods We linked Medicare claims data from 2007 to 2014 with a multicenter electronic health records system. The study cohort comprised patients ≥65 years with atrial fibrillation and venous thromboembolism initiating warfarin. We compared results when defining warfarin discontinuation by (1) different gaps (3, 7, 14, 30, and 60 days) between dispensings and (2) having a gap ≤60 days or bridging larger gaps if there was INR ordering at least every 42 days (60_INR). Discontinuation was considered misclassified if there was an INR ≥2 within 7 days after the discontinuation date. Results Among 3,229 patients, a shorter gap resulted in a shorter mean follow-up time (82, 95, 117, 159, 196, and 259 days for gaps of 3, 7, 14, 30, 60, and 60_INR, respectively; p < 0.001). Incorporating INR (60_INR) can reduce misclassification of warfarin discontinuation from 68 to 4% (p < 0.001). The on-treatment risk estimation of clinical endpoints varied significantly by discontinuation definitions. Conclusion Using a short gap between warfarin dispensings to define discontinuation may lead to substantial misclassification, which can be improved by incorporating intervening INR codes.

中文翻译：

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使用简单的处方差异来确定华法林停药可能会导致严重的错误分类


背景 华法林仍然广泛使用，并且是其他直接口服抗凝剂研究中的关键比较药物。由于通常会提供比所需时间更长的华法林处方，以便根据国际标准化比率 (INR) 进行剂量调整，因此使用配药之间允许的较短间隔来定义华法林停药的常见做法可能会导致华法林暴露的严重错误分类。我们的目的是量化这种错误分类并确定定义华法林停药的最佳算法。方法 我们将 2007 年至 2014 年的医疗保险索赔数据与多中心电子健康记录系统关联起来。研究队列由年龄≥65岁且患有心房颤动和静脉血栓栓塞且开始使用华法林的患者组成。我们比较了定义华法林停药的结果：(1) 配药之间的不同间隔（3、7、14、30 和 60 天）；(2) 间隔≤60 天，或者如果至少每一次都有 INR 订购，则弥合更大的间隔42 天 (60_INR)。如果停药日期后 7 天内 INR ≥2，则认为停药分类错误。结果 在 3,229 名患者中，较短的间隙导致较短的平均随访时间（对于 3、7、14、30、60 和 60_INR 的间隙，分别为 82、95、117、159、196 和 259 天；p < 0.001）。纳入 INR (60_INR) 可以将华法林停药的错误分类从 68% 减少到 4% (p < 0.001)。临床终点的治疗风险评估因停药定义而异。结论 使用华法林配药之间的短暂间隔来定义停药可能会导致严重的错误分类，这可以通过纳入干预 INR 代码来改善。