Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Department of Clinical Science and Education at Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
J Thromb Haemost. 2017 Mar;15(3):446-453. doi: 10.1111/jth.13614. Epub 2017 Feb 17.
Essentials Data on the effect of introducing amiodarone in patients already using warfarin regime are scarce. Information on 754 patients was extracted from three nationwide registers in Sweden. With amiodaron, 37% of patients had an international normalized ratio (INR) over 3.0 To avoid bleeding, the initiation of amiodarone should be accompanied by closer INR monitoring.
Background Data indicate that the interaction between warfarin and amiodarone results in an increased warfarin effect. There are several large, well-performed studies using genetic and clinical factors such as co-medication to predict an adequate starting dose of warfarin. However, longitudinal data on the effect of introducing amiodarone in patients on an ongoing warfarin regime are more scarce. Objectives An investigation of how initiation of amiodarone affects the anticoagulant effect and dosing of warfarin, using data from three nationwide registries. Patients/Methods In a retrospective cohort study including 754 patients, warfarin doses were compared between two 4-week periods, before and 18-21 weeks after initiating co-treatment with amiodarone. In addition, warfarin doses and international normalized ratio (INR) values were calculated week-by-week after the initiation of amiodarone. Results The initiation of amiodarone increased the mean INR from 2.6 to 3.1. The proportion of patients with a supratherapeutic INR over 3.0 and 4.0 increased from 12% to 37% and 0.9% to 5.5%, respectively. The subsequent mean decrease in warfarin dose was 24.6% (95% confidence interval [CI], 23.5, 25.6). The frequency of INR monitoring within 1 and 2 weeks after initiation of amiodarone was 67% and 90%. Conclusions Although warfarin doses in most patients were within the therapeutic range, more than one in three patients initiating co-treatment with amiodarone were exposed to a supratherapeutic anticoagulative effect within 3 weeks. In order to further avoid severe unnecessary bleeding, the initiation of amiodarone should be accompanied by closer INR monitoring, anticipating an average dose reduction of 25%.
现有数据表明，华法林与胺碘酮相互作用会增强华法林的效果。已有多项大型、设计良好的研究使用基因和临床因素（如合并用药）来预测华法林起始的适当剂量。然而，在持续华法林治疗方案中，胺碘酮的引入对其抗凝效果和华法林剂量的影响的纵向数据更为稀缺。目的：利用来自三个全国性登记处的数据，调查胺碘酮的引入如何影响华法林的抗凝效果和剂量。
患者/方法：在一项包括 754 例患者的回顾性队列研究中，比较了在开始胺碘酮联合治疗的前后两个 4 周期间的华法林剂量。此外，在开始胺碘酮后每周计算华法林剂量和国际标准化比值（INR）值。
胺碘酮的引入使平均 INR 从 2.6 升高至 3.1。INR 超过 3.0 和 4.0 的患者比例从 12%增加至 37%和 0.9%增加至 5.5%。随后，华法林剂量平均减少了 24.6%（95%置信区间[CI]：23.5%，25.6%）。在开始胺碘酮后 1 周和 2 周内，INR 监测的频率分别为 67%和 90%。
尽管大多数患者的华法林剂量仍在治疗范围内，但超过三分之一开始联合胺碘酮治疗的患者在 3 周内出现了抗凝过度的情况。为了进一步避免严重的不必要出血，胺碘酮的引入应伴随更密切的 INR 监测，预计平均剂量减少 25%。
