Mayo Clinic School of Medicine, Mayo Clinic, Rochester, Minnesota.
Division of Hematology, Oregon Health & Science University, Portland, Oregon.
Eur J Haematol. 2019 Jul;103(1):43-46. doi: 10.1111/ejh.13240. Epub 2019 May 6.
Direct oral anticoagulants (DOACs) are being increasingly used. However, unlike warfarin, less is known regarding their long-term side effects. To better evaluate the rates of DOAC-related adverse events (AEs) on a population level, we examined AEs reported to the FDA for three commonly used DOACs and warfarin.
We evaluated the FDA Adverse Event Reporting System (FAERS) database, which compiles reported drug-related AEs from 1969 onwards. The safety profiles of the included drugs were assessed by comparing AEs per outpatient prescription and with proportional reporting ratios (PRR).
Rivaroxaban had the highest proportion of reported AEs. Most notably the rate for breakthrough venous thromboembolism (VTE) was higher than other DOACs. Dabigatran had the highest reported rates of ischemic stroke. When the DOAC data were analyzed using PRR, reported rates of VTE were again higher with rivaroxaban while dabigatran again showed slightly higher than expected rates of ischemic stroke. Apixaban did not show higher than expected rates in any category.
Our analysis found rates of reported breakthrough VTE were significantly higher with rivaroxaban, while apixaban had no higher than expected rates of any studied AEs.
直接口服抗凝剂（DOAC）的应用日益增多。然而，与华法林不同，人们对其长期副作用的了解较少。为了更全面地评估人群中 DOAC 相关不良事件（AE）的发生率，我们研究了 FDA 对三种常用 DOAC 和华法林的不良事件报告。
我们评估了 FDA 不良事件报告系统（FAERS）数据库，该数据库从 1969 年起汇编了与药物相关的不良事件报告。通过比较门诊处方中的不良事件发生率和比例报告比（PRR）来评估纳入药物的安全性概况。
利伐沙班的不良事件报告比例最高。值得注意的是，突破性静脉血栓栓塞（VTE）的发生率高于其他 DOAC。达比加群的缺血性卒中报告率最高。当使用 PRR 分析 DOAC 数据时，利伐沙班的 VTE 报告率再次较高，而达比加群的缺血性卒中报告率也略高于预期。阿哌沙班在任何类别中均未显示出高于预期的发生率。
我们的分析发现，利伐沙班的突破性 VTE 报告率显著较高，而阿哌沙班的任何研究 AE 发生率均未高于预期。
