Zhang Yumao, Souverein Patrick C, Gardarsdottir Helga, van den Ham Hendrika A, Maitland-van der Zee Anke-Hilse, de Boer Anthonius
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Department of Pharmacy, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
Br J Clin Pharmacol. 2020 Jun;86(6):1150-1164. doi: 10.1111/bcp.14227. Epub 2020 Feb 21.
To assess the association between concurrent use of potential pharmacokinetic or pharmacodynamic interacting drugs and major bleeding among direct oral anticoagulant (DOAC) users.
We performed a case-control study nested in a cohort of new users of DOACs (dabigatran etexilate, apixaban or rivaroxaban). Data were obtained from the UK Clinical Practice Research Datalink linked to Hospital Episode Statistics (2008-2015). Cases were patients hospitalized having a primary diagnosis of major bleeding. Up to 4 controls were matched on age, sex, index date and region. Odds ratios (ORs) for the risk of major bleeding were assessed by conditional logistic regression analysis and adjusted for well-known covariates for the risk of bleeding.
We identified 393 patients with a major bleeding from a total of 23 492 new users of DOACs and 1494 matched controls. Most subjects were users of rivaroxaban (58.8%) on the index date. The concurrent use of pharmacodynamic interacting drugs was associated with an increased risk of major bleeding (21.6% of cases vs 13.5% of controls, adjusted odds ratio [aOR] 1.92; 95% confidence interval [CI], 1.40-2.66). For the antiplatelet drugs the aOR was 2.01 (95% CI, 1.29-3.11) and for the selective serotonin reuptake inhibitors the aOR was 1.68 (95% CI, 1.10-2.59). We found no increased risk of major bleeding for concurrent use of pharmacokinetic interacting drugs vs DOACs alone (45.0 vs 51.2%; aOR: 0.77; 95% CI: 0.53-1.10).
Among patients taking DOACs the concurrent use of antiplatelet drugs or selective serotonin reuptake inhibitors was associated with increased risk of major bleeding, while pharmacokinetic interacting drugs do not increase this risk.
评估直接口服抗凝剂（DOAC）使用者同时使用具有潜在药代动力学或药效学相互作用的药物与大出血之间的关联。
我们在一组DOAC新使用者（达比加群酯、阿哌沙班或利伐沙班）中进行了一项巢式病例对照研究。数据来自与医院事件统计数据（2008 - 2015年）相链接的英国临床实践研究数据链。病例为初步诊断为大出血而住院的患者。按年龄、性别、索引日期和地区匹配最多4名对照。通过条件逻辑回归分析评估大出血风险的比值比（OR），并针对已知的出血风险协变量进行调整。
在总共23492名DOAC新使用者和1494名匹配对照中，我们识别出393名大出血患者。在索引日期，大多数受试者是利伐沙班使用者（58.8%）。同时使用药效学相互作用药物与大出血风险增加相关（病例组为21.6%，对照组为13.5%，调整后比值比[aOR]为1.92；95%置信区间[CI]为1.40 - 2.66）。抗血小板药物的aOR为2.01（95%CI为1.29 - 3.11），选择性5-羟色胺再摄取抑制剂的aOR为1.68（95%CI为1.10 - 2.59）。我们发现，与单独使用DOAC相比，同时使用药代动力学相互作用药物并未增加大出血风险（分别为45.0%和51.2%；aOR：0.77；95%CI：0.53 - 1.10）。
在服用DOAC的患者中，同时使用抗血小板药物或选择性5-羟色胺再摄取抑制剂与大出血风险增加相关，而药代动力学相互作用药物不会增加此风险。
