Oates A, Jackson P R, Austin C A, Channer K S
Department of Cardiology, Royal Hallamshire Hospital, Sheffield.
Br J Clin Pharmacol. 1998 Aug;46(2):157-61. doi: 10.1046/j.1365-2125.1998.00755.x.
Oral anticoagulation is increasingly used in elderly patients with atrial fibrillation to prevent embolic phenomena. The use of anticoagulants in this population is prophylactic rather than therapeutic and so there is no urgency to establish anticoagulation within the desired therapeutic range. The aim of the study was to develop an out-patient regimen for initiation of oral anticoagulation with warfarin which requires only weekly monitoring of the International Normalized Ratio (INR).
The study was undertaken in two phases. In the first phase, factors which predict the final maintenance dosage of warfarin were defined and used to build a decision tree and dosage algorithm. In the second study the algorithm was tested. Patients were given 2 mg warfarin daily for 2 weeks and the INR at this time was used to predict the maintenance dose. Patients then attended for weekly measurements of the INR until steady state had been reached. Dosage adjustments were not made unless the INR was >4.0 or <1.5 for 2 consecutive weeks. The accuracy of the prediction was measured by calculating the mean INR of weeks 6-8 and the number of patients in the target range 2.0-3.0 was determined.
One hundred and seven consecutive out-patients (mean age 70 years range 64-86) completed the first study. The age, sex, height, weight, alcohol intake, number of cigarettes smoked, concomitant medication, clinical evidence of right heart failure, liver failure, abnormalities in liver enzyme estimations, baseline INR and INR after 2 weeks of 2 mg warfarin daily were used in a polytomous logistic regression analysis with stepwise inclusion of factors to determine which factors influenced the eventual maintenance dosage of warfarin. The INR after 2 weeks of 2 mg warfarin therapy predicted 70% of the variability of the maintenance dose. Of other factors only the sex of the patient had a large enough effect to be included in the prediction algorithm. One hundred and six patients (mean age 71 years range 50-85 years) completed the second study. Only one patient needed a dose adjustment in the first 2 weeks of warfarin 2 mg daily (INR 4.4). Overall, 60% patients were in the narrow target range (INR 2.0-3.0) at steady state. In five patients the INR was >4.0 at any visit after the second week and needed dosage adjustment. In four patients the INR was <1.5 at steady state.
We have developed a method of predicting the maintenance dose of warfarin in an elderly population based on the INR after 2 weeks of warfarin 2 mg daily, and the sex of the patient. This is a safe and convenient way of initiating warfarin therapy as an out-patient which requires only weekly INR checks.
口服抗凝药越来越多地用于老年房颤患者以预防栓塞现象。在这一人群中使用抗凝药是预防性的而非治疗性的，因此无需急于将抗凝作用确立在期望的治疗范围内。本研究的目的是制定一种门诊华法林口服抗凝起始方案，该方案仅需每周监测国际标准化比值（INR）。
本研究分两个阶段进行。在第一阶段，确定预测华法林最终维持剂量的因素，并用于构建决策树和剂量算法。在第二项研究中对该算法进行测试。患者每天服用2mg华法林，持续2周，此时的INR用于预测维持剂量。然后患者每周前来测量INR，直至达到稳定状态。除非INR连续2周>4.0或<1.5否则不进行剂量调整。通过计算第6 - 8周的平均INR来衡量预测的准确性，并确定处于目标范围2.0 - 3.0的患者数量。
107例连续门诊患者（平均年龄70岁，范围64 - 86岁）完成了第一项研究。将年龄、性别、身高、体重、酒精摄入量、吸烟数量、合并用药、右心衰竭的临床证据、肝功能衰竭、肝酶估计值异常、基线INR以及每天服用2mg华法林2周后的INR用于多分类逻辑回归分析，逐步纳入因素以确定哪些因素影响华法林的最终维持剂量。每天服用2mg华法林2周后的INR预测了维持剂量70%的变异性。在其他因素中，只有患者性别对预测算法有足够大的影响而被纳入。106例患者（平均年龄71岁，范围50 - 85岁）完成了第二项研究。在每天服用2mg华法林的前2周，只有1例患者需要调整剂量（INR为4.4）。总体而言，60% 的患者在稳定状态时处于狭窄的目标范围（INR 2.0 - 3.0）。在5例患者中，第二周后的任何一次就诊时INR>4.0，需要调整剂量；在4例患者中，稳定状态时INR<1.5。
我们已经开发出一种基于每天服用2mg华法林2周后的INR以及患者性别的方法来预测老年人群中华法林的维持剂量方法。这是一种安全且方便的门诊启动华法林治疗的方法，仅需每周检查INR。
