The real world use of combined P-glycoprotein and moderate CYP3A4 inhibitors with rivaroxaban or apixaban increases bleeding
The real world use of combined P-glycoprotein and moderate CYP3A4 inhibitors with rivaroxaban or apixaban increases bleeding
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DOI：
10.1007/s11239-020-02037-3
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发表时间：
2020-05-01
影响因子：
4
通讯作者：
Dorsch, Michael P.
中科院分区：
文献类型：
--
作者：
Hanigan, Sarah;Das, Jessica;Dorsch, Michael P.
使用直接口服抗凝剂预防心房颤动中风的情况持续增加。某些人群可能面临更高的药物暴露和不良事件风险。药代动力学研究表明，联合使用 P-gp 和中度 CYP3A4 抑制剂时，利伐沙班和阿哌沙班的暴露量增加，但其临床相关性尚不清楚。这项回顾性队列研究包括2012年1月1日至2016年12月31日期间接受利伐沙班或阿哌沙班联合中度抑制剂（胺碘酮、决奈达隆、地尔硫卓、维拉帕米）至少3个月的药物-药物相互作用（DDI）组患者。倾向匹配用于识别不存在 DDI 的类似对照患者。主要结局是国际血栓与止血学会定义的任何出血事件的事件发生时间分析。经过倾向匹配后，每组均纳入 213 名具有相似基线特征的患者。平均 CHA2DS2-VASc 评分为 3.0，中位随访时间为 1.45 年。主要结局发生在 DDI 组 26.4% 的患者和对照组 18.4% 的患者中（风险比 1.8，95% 置信区间 [CI] 1.19 至 2.73；p 值 = 0.006）。不同抑制剂类型的出血率没有差异。在这项现实世界的回顾性研究中，与未使用 DDI 的患者相比，联合使用 P-gp 和中效 CYP3A4 抑制剂与利伐沙班或阿哌沙班会增加出血风险。需要对更大的患者群体进行分析来证实这些发现。
The use of direct oral anticoagulants for stroke prevention in atrial fibrillation continues to rise. Certain populations may be at higher risk for increased drug exposure and adverse events. Pharmacokinetic studies suggest increased exposure of rivaroxaban and apixaban with combined P-gp and moderate CYP3A4 inhibitors but the clinical relevance of this is unknown. This retrospective cohort study included patients receiving rivaroxaban or apixaban from January 1, 2012 to December 31, 2016 with a moderate inhibitor (amiodarone, dronedarone, diltiazem, verapamil) for at least 3 months in the drug-drug interaction (DDI) group. Propensity matching was used to identify similar control patients without the presence of the DDI. The primary outcome was a time to event analysis of any bleeding episode as defined by the International Society of Thrombosis and Hemostasis. After propensity matching, 213 patients with similar baseline characteristics were included in each group. The mean CHA2DS2-VASc score was 3.0 and median duration of follow-up was 1.45 years. The primary outcome occurred in 26.4% of patients in the DDI group and 18.4% in the control group (hazard ratio 1.8, 95% confidence interval [CI] 1.19 to 2.73; p-value = 0.006). There was no difference in bleeding rates based on type of inhibitor. Use of a combined P-gp and moderate CYP3A4 inhibitor with rivaroxaban or apixaban increased bleeding risk compared to patients without the DDI in this real world, retrospective study. Analysis in a larger patient population is needed to confirm these findings.