Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan.
Clin Drug Investig. 2019 Jul;39(7):665-670. doi: 10.1007/s40261-019-00788-3.
The development of new oral anticoagulants (NOACs) has led to an alternative to treatment with warfarin. However, real-world data on comparing safety profiles of NOACs and warfarin are insufficient.
The purpose of this study was to compare safety profiles of warfarin and NOACs using a spontaneous reporting system database.
Adverse event reports spontaneously submitted to the Pharmaceuticals and Medical Devices Agency (Japan) between April 2011 and January 2017 were analysed. We performed disproportionality analyses, calculating the reporting odds ratio (ROR) with 95% confidence interval (CI).
The database comprised 3445 reports associated with warfarin, and 14,269 reports with NOACs. A large number of bleeding complications were detected with the use of both warfarin and NOACs. As for cerebral haemorrhage, the signal scores were greater for NOACs as a class (ROR 25.1, 95% CI 23.3-27) and individual agents (edoxaban: ROR 23.6, 95% CI 18.6-29.9; rivaroxaban ROR 23.9, 95% CI 21.4-26.8; apixaban ROR 28.1, 95% CI 25.4-31.1) than for warfarin (ROR 18.9, 95% CI 16.4-21.7), but showed the lowest value for dabigatran (ROR 9.26, 95% CI 7.76-11). Gastrointestinal haemorrhage had stronger signals for NOACs (ROR 19.4, 95% CI 17.8-21.1) than warfarin (ROR 12.2, 95% CI 10.2-14.6). With respect to calciphylaxis, the association with warfarin was noteworthy (ROR 190; 95% CI, 126-287), but no reports were detected involving NOACs.
Our results may provide useful information for treatment with oral anticoagulants, although further studies with more data are needed.
新型口服抗凝剂（NOACs）的发展为华法林治疗提供了替代方案。然而，关于比较 NOACs 和华法林安全性的真实世界数据还不够。
本研究旨在使用自发报告系统数据库比较华法林和 NOACs 的安全性。
分析 2011 年 4 月至 2017 年 1 月期间向日本药品和医疗器械管理局（Pharmaceuticals and Medical Devices Agency，PMDA）自发提交的不良事件报告。我们进行了不相称性分析，计算了报告比值比（ROR）及其 95%置信区间（CI）。
该数据库包含 3445 例与华法林相关的报告和 14269 例与 NOACs 相关的报告。华法林和 NOACs 均检测到大量出血并发症。对于脑出血，NOACs 类别的信号评分更高（ROR 25.1，95%CI 23.3-27）和个别药物（依度沙班：ROR 23.6，95%CI 18.6-29.9；利伐沙班：ROR 23.9，95%CI 21.4-26.8；阿哌沙班：ROR 28.1，95%CI 25.4-31.1），而华法林的信号评分较低（ROR 18.9，95%CI 16.4-21.7），但达比加群的评分最低（ROR 9.26，95%CI 7.76-11）。胃肠道出血的信号强度高于华法林（ROR 19.4，95%CI 17.8-21.1）。对于钙化醇血症，与华法林的关联值得注意（ROR 190；95%CI，126-287），但未检测到与 NOACs 相关的报告。
尽管需要更多数据的进一步研究，但我们的结果可能为口服抗凝治疗提供有用的信息。
