Department of Hospital Pharmacy, Tjongerschans Heerenveen, Thialfweg 44, 8448 SB, Heerenveen, The Netherlands.
Netherlands Pharmacovigilance Centre Lareb, Lareb, The Netherlands.
Clin Drug Investig. 2022 Jul;42(7):593-598. doi: 10.1007/s40261-022-01165-3. Epub 2022 Jun 8.
Several cases of venous thromboembolism in patients treated with direct oral anticoagulants (DOACs) have been reported in the literature, but a quantative analysis of postmarketing reports is lacking. The objective of this study was to determine the post-marketing odds ratio (OR) and reporting odds ratio (ROR) of venous thromboembolism in patients receiving DOACs compared among each other and to vitamin K antagonists (VKAs).
The OR and ROR were used to determine the ratio of reports for deep vein thrombosis and pulmonary embolism between 1 January, 2012 and 15 November, 2020 using the World Health Organization VigiLyze database. This was performed using all venous thromboembolism events in which a DOAC or a VKA was the suspected medication. The OR and ROR including 95% confidence intervals were calculated for each DOAC drug in comparison to all VKAs as a group.
The OR of deep vein thrombosis was highest for rivaroxaban compared with dabigatran and apixaban [2.63 (2.41-2.89); 1.84 (1.72-1.97)]. The OR of deep vein thrombosis was lowest for edoxaban compared with dabigatran, apixaban and rivaroxaban [0.44 (0.32-0.61); 0.31 (0.22-0.42); 0.17 (0.12-0.23)]. The OR of pulmonary embolism was also highest for rivaroxaban compared with dabigatran and apixaban [2.59 (2.37-2.83); 1.79 (1.68-1.92)]. The OR of pulmonary embolism was also lowest for edoxaban compared with dabigatran, apixaban and rivaroxaban [0.77 (0.60-0.97); 0.59 (0.41-0.67); 0.30 (0.23-0.37)]. Comparing RORs of various DOACs with VKAs, rivaroxaban had the highest RORs for deep vein thrombosis/pulmonary embolism, in comparison to apixaban, dabigatran and edoxaban.
Our findings may indicate a higher association between rivaroxaban therapy and venous thromboembolism as compared with apixaban, dabigatran and edoxaban. These findings are uncertain owing to the reliability of a post-marketing registration system that is negatively influenced by a high level of under-reporting. However, based on pharmacodynamics, we cannot exclude the possibility that there is a real effect that may be driven by non-adherence.
已有文献报道了数例接受直接口服抗凝剂（DOACs）治疗的患者发生静脉血栓栓塞症（venous thromboembolism，VTE）的病例，但缺乏上市后报告的定量分析。本研究旨在确定与维生素 K 拮抗剂（VKA）相比，接受 DOAC 治疗的患者 VTE 的上市后比值比（odds ratio，OR）和报告比值比（reporting odds ratio，ROR）。
使用世界卫生组织的 VigiLyze 数据库，采用 OR 和 ROR 于 2012 年 1 月 1 日至 2020 年 11 月 15 日期间，确定 DOAC 与 VKA 相比，深静脉血栓形成（deep vein thrombosis，DVT）和肺栓塞（pulmonary embolism，PE）的报告率。对每例 DVT 或 PE 事件中可疑药物为 DOAC 或 VKA 的患者进行分析。对每个 DOAC 药物与所有 VKA 进行比较，计算 OR 和 ROR，以 95%置信区间表示。
与达比加群和阿哌沙班相比，利伐沙班发生 DVT 的 OR 最高[2.63（2.41-2.89）；1.84（1.72-1.97）]。与达比加群、阿哌沙班和利伐沙班相比，依度沙班发生 DVT 的 OR 最低[0.44（0.32-0.61）；0.31（0.22-0.42）；0.17（0.12-0.23）]。与达比加群和阿哌沙班相比，利伐沙班发生 PE 的 OR 也最高[2.59（2.37-2.83）；1.79（1.68-1.92）]。与达比加群、阿哌沙班和利伐沙班相比，依度沙班发生 PE 的 OR 也最低[0.77（0.60-0.97）；0.59（0.41-0.67）；0.30（0.23-0.37）]。与 VKA 相比，比较各种 DOAC 的 ROR，利伐沙班的 DVT/PE 的 ROR 最高，阿哌沙班、达比加群和依度沙班的 ROR 较低。
与阿哌沙班、达比加群和依度沙班相比，我们的研究结果可能表明利伐沙班治疗与 VTE 之间存在更高的相关性。由于上市后登记系统的可靠性受到低报告率的负面影响，因此这些发现并不确定。但是，根据药代动力学，我们不能排除可能存在真正的效果，这可能是由不遵医嘱引起的。
