Gaio Mario, Ferrajolo Carmen, Zinzi Alessia, Riccardi Consiglia, Di Filippo Pasquale, Carangelo Ludovica, Pieretti Gorizio, Rossi Francesco, Nicoletti Giovanni Francesco, Capuano Annalisa
Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, University of Campania "Luigi Vanvitelli", Department of Experimental Medicine, Napoli, Italy.
Plastic Surgery Unit, University of Campania "Luigi Vanvitelli", Multidisciplinary Department of Medical Surgical and Dental Sciences, Napoli, Italy.
Front Pharmacol. 2021 Dec 7;12:790740. doi: 10.3389/fphar.2021.790740. eCollection 2021.
Post-marketing data on the risks associated with direct oral anticoagulants (DOACs) are conflicting and only few studies evaluated a comparison between each different DOAC. Real-world data from pharmacovigilance databases can help to better define the safety profile of each DOAC and warfarin. However, Correspondence Analysis (CA) could represent a useful tool in this context. In the attempt to assess the usefulness of CA as a signal detection pharmacovigilance tool, we applied this method to the Italian Pharmacovigilance Database (RNF, ), by comparing with disproportionality analysis on warfarin and DOACs. Study based on AEs sent to RNF by Campania Region from 2008 to 2021, in which warfarin, dabigatran, apixaban, edoxaban or rivaroxaban were reported as suspected drug. AEs were clustered into three Standardized MedDRA Queries (SMQs): Central Nervous System Haemorrhages and Conditions (CNSH), GastroIntestinal Perforation, Ulceration, Obstruction or Haemorrhages (GIPUOH) and other Haemorrhages (HH). Non-haemorrhagic AEs were included in a fourth cluster (nHH). We retrieved 1,161 reports: 41.5% are associated to warfarin, 21.0% to dabigatran, 17.8% to rivaroxaban, 13.9% to apixaban and 5.8% to edoxaban. No significant differences in age distribution were observed. Results of CA showed that dabigatran and warfarin have the highest contribution (44.910 and 47.656, respectively) to the inertia of Dimension 1 as well as apixaban and dabigatran to the inertia of Dimension 2 (53.768 and 30.488, respectively). Edoxaban and rivaroxaban showed a negligible total contribution. CA biplot showed positive associations between warfarin and HH, apixaban and CNSH and dabigatran and nHH. Results seem to confirm that DOACs are not interchangeable. Apixaban was surprisingly associated with a higher risk of cerebral haemorrhage. As expected, our data support the better safety profile of DOACs than warfarin in terms of skin and respiratory tract hemorrhagic risks. Finally, we showed how CA could play a complementary role in analyzing data from pharmacovigilance databases.
关于直接口服抗凝剂（DOACs）相关风险的上市后数据相互矛盾，仅有少数研究对不同DOAC之间进行了比较。来自药物警戒数据库的真实世界数据有助于更好地明确每种DOAC和华法林的安全性概况。然而，对应分析（CA）在这方面可能是一种有用的工具。为了评估CA作为一种信号检测药物警戒工具的实用性，我们将该方法应用于意大利药物警戒数据库（RNF），并与华法林和DOACs的不成比例分析进行比较。该研究基于坎帕尼亚地区在2008年至2021年期间发送至RNF的不良事件，其中华法林、达比加群、阿哌沙班、依度沙班或利伐沙班被报告为可疑药物。不良事件被聚类为三个标准化医学术语词典查询（SMQ）：中枢神经系统出血及病症（CNSH）、胃肠道穿孔、溃疡、梗阻或出血（GIPUOH）以及其他出血（HH）。非出血性不良事件被纳入第四个聚类（nHH）。我们检索到1161份报告：41.5%与华法林相关，21.0%与达比加群相关，17.8%与利伐沙班相关，13.9%与阿哌沙班相关，5.8%与依度沙班相关。未观察到年龄分布存在显著差异。CA结果显示，达比加群和华法林对第1维度的惯性贡献最高（分别为44.910和47.656），阿哌沙班和达比加群对第2维度的惯性贡献最高（分别为53.768和30.488）。依度沙班和利伐沙班的总贡献可忽略不计。CA双标图显示华法林与HH、阿哌沙班与CNSH以及达比加群与nHH之间存在正相关。结果似乎证实DOACs不可相互替代。阿哌沙班与脑出血风险较高令人惊讶地相关。正如预期的那样，我们的数据支持DOACs在皮肤和呼吸道出血风险方面比华法林具有更好的安全性概况。最后，我们展示了CA在分析药物警戒数据库数据时如何发挥补充作用。
Zotero 插件
