Caldeira Daniel, Rodrigues Raquel, Abreu Daisy, Anes Ana Marta, Rosa Mário M, Ferreira Joaquim J
a Laboratório de Farmacologia Clínica e Terapêutica, Faculdade de Medicina , Universidade de Lisboa , Lisbon , Portugal.
b Instituto de Medicina Molecular, Faculdade de Medicina , Universidade de Lisboa , Lisbon , Portugal.
Expert Opin Drug Saf. 2018 Apr;17(4):339-345. doi: 10.1080/14740338.2018.1439474. Epub 2018 Feb 20.
In this pharmacovigilance study, we aimed to determine the incidence of spontaneously reported suspected adverse drug reactions (ADRs) related to oral anticoagulants: non-vitamin K antagonist oral anticoagulants (NOACs; apixaban, dabigatran, edoxaban, rivaroxaban) and vitamin K antagonists (VKA) Research design and methods: In this retrospective observational study, we extracted all the individual case safety reports related to oral anticoagulants recorded in the Portuguese Pharmacovigilance Database (January 2010 to April 2015). The annual incidence of suspected ADRs was estimated using drug exposure data. Disproportionality of reporting ADR was addressed through reporting odds ratio (ROR) and 99% confidence intervals.
We appraised 794 suspected ADR (78% related to NOACs). The annual number of ADRs increased overtime with 9 ADRs/million Defined Daily Dose (DDD) at the end of 2014. The incidence of NOACs ADRs decreased from 2012 onwards. VKA showed a disproportion in 'Investigation' (ROR 0.10, 99%CI 0.05-0.22) and 'Injury, poisoning and procedural complications' (ROR 0.36, 99%CI 0.19-0.69) ADRs compared with NOACs. NOACs had a higher significant disproportion of 'Nervous system disorders' related ADRs (ROR 3.98, 99%CI 1.50-10.53).
Reporting of ADRs associated with oral anticoagulants (mainly NOACs), is increasing. Exploratory disproportion analyses showed an increase of reports of nervous system ADRs with NOACs, and INR-related ADRs with VKA.
在这项药物警戒研究中，我们旨在确定自发报告的与口服抗凝剂相关的疑似药物不良反应（ADR）的发生率：非维生素K拮抗剂口服抗凝剂（NOACs；阿哌沙班、达比加群、依度沙班、利伐沙班）和维生素K拮抗剂（VKA）。研究设计与方法：在这项回顾性观察研究中，我们提取了葡萄牙药物警戒数据库（2010年1月至2015年4月）中记录的所有与口服抗凝剂相关的个体病例安全报告。使用药物暴露数据估计疑似ADR的年发生率。通过报告比值比（ROR）和99%置信区间来处理ADR报告的不成比例性。
我们评估了794例疑似ADR（78%与NOACs相关）。ADR的年数量随时间增加，2014年底为每百万限定日剂量（DDD）9例ADR。从2012年起，NOACs的ADR发生率下降。与NOACs相比，VKA在“检查”（ROR 0.10，99%CI 0.05 - 0.22）和“损伤、中毒及操作并发症”（ROR 0.36，99%CI 0.19 - 0.69）ADR方面表现出不成比例性。NOACs在与“神经系统疾病”相关的ADR方面有更高的显著不成比例性（ROR 3.98，99%CI 1.50 - 10.53）。
与口服抗凝剂（主要是NOACs）相关的ADR报告正在增加。探索性的不成比例分析显示，NOACs的神经系统ADR报告增加，VKA的与国际标准化比值（INR）相关的ADR报告增加。
