Department of Clinical Pharmacology, Copenhagen University Hospital Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Copenhagen Phase IV Unit (Phase4Cph), Copenhagen University Hospital Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Drug Saf. 2022 Apr;45(4):379-388. doi: 10.1007/s40264-022-01147-6. Epub 2022 Mar 19.
In Denmark, physicians are legally obliged to report serious adverse drug reactions (ADRs), such as intracranial hemorrhage (ICH) following anticoagulant (AC) treatment, to the Danish Medicines Agency. We were therefore puzzled to discover a high number of reports concerning ICHs following treatment with the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban, and apixaban compared with warfarin. This was surprising, as all DOACs have been found to be associated with a lower risk of ICH compared with warfarin in phase III randomized controlled trials.
The primary aim of the study was to estimate the level of underreporting of ICH as an ADR following treatment with warfarin, dabigatran, rivaroxaban, and apixaban.
This observational study covered a 5-year period (2014-2018). Using nationwide registries held by the Danish Health Data Authority, the number of users, exposure time in person-years, and related ICH events for each of the study drugs were estimated. Data on ADR-ICH reports were extracted from the interactive ADR overviews held by the Danish Medicines Agency.
From 2014 to 2018, 97.0% of the identified warfarin-related ICH events were not reported as ADRs. For the DOACs, the level of underreporting ranged from 88.8 to 90.8%.
We found a heavy and differentiated level of underreporting of ICH as an ADR following treatment with the four study drugs.
在丹麦，医生有法律义务向丹麦药品管理局报告严重药物不良反应（ADR），如抗凝（AC）治疗后颅内出血（ICH）。因此，我们发现与华法林相比，直接口服抗凝剂（DOAC）达比加群、利伐沙班和阿哌沙班治疗后ICH 的报告数量较高，这令人困惑。这令人惊讶，因为在 III 期随机对照试验中，所有 DOAC 与华法林相比，ICH 的风险都较低。
本研究的主要目的是估计华法林、达比加群、利伐沙班和阿哌沙班治疗后 ICH 作为 ADR 的漏报水平。
本观察性研究涵盖了 5 年（2014-2018 年）。使用丹麦健康数据局持有的全国性登记册，估计了每种研究药物的使用者数量、个体人年暴露时间和相关 ICH 事件。ADR-ICH 报告的数据从丹麦药品管理局的互动 ADR 概览中提取。
从 2014 年到 2018 年，97.0%的确定与华法林相关的 ICH 事件未作为 ADR 报告。对于 DOAC，漏报率范围为 88.8%至 90.8%。
我们发现四种研究药物治疗后 ICH 作为 ADR 的漏报程度严重且存在差异。
