Department of Pharmacy, Houston Methodist Hospital, Houston, TX, USA.
Department of Pharmacy, Houston Methodist Willowbrook Hospital, Houston, TX, USA.
J Oncol Pharm Pract. 2020 Oct;26(7):1650-1656. doi: 10.1177/1078155220901777. Epub 2020 Feb 16.
Venous thromboembolism is a common complication among cancer patients with an estimated risk of 20%. American Society of Clinical Oncology guidelines recommend direct oral anticoagulants for long-term anticoagulation but caution the use of direct oral anticoagulants because of drug-drug interactions with antineoplastic therapies. The clinical impact of these drug-drug interactions is yet to be studied in clinical trials. This study aims to evaluate the effect of the drug-drug interactions on venous thromboembolism recurrence and bleeding.
This is a retrospective cohort study that included cancer patients with venous thromboembolism receiving apixaban or rivaroxaban with antineoplastic therapy. The impact of the drug-drug interaction was determined by its effect on the rates of venous thromboembolism recurrence and bleeding in patients with a drug-drug interaction compared to patients with no drug-drug interaction.
The primary composite endpoint of venous thromboembolism recurrence and bleeding events occurred in 65% versus 62% of patients in drug-drug interaction and non-drug-drug interaction groups accordingly. There was a higher rate of venous thromboembolism recurrence and minor bleeding events with anti-mitotic microtubule inhibitors and a higher rate of minor bleeding events with hormonal therapy and alkylating agents. Among the drug-drug interaction group, there were no major bleeding events reported with mild drug-drug interactions when compared to moderate-to-severe drug-drug interactions. There was no difference in time to venous thromboembolism recurrence between rivaroxaban and apixaban.
Due to small sample size, our study results could not confirm a higher risk of bleeding or venous thromboembolism recurrence with the drug-drug interactions. Further prospective study is warranted, but clinicians should be aware of these drug-drug interactions and identify them using available literature.
静脉血栓栓塞是癌症患者的常见并发症,估计风险为 20%。美国临床肿瘤学会指南建议使用直接口服抗凝剂进行长期抗凝治疗,但由于与抗肿瘤治疗的药物相互作用,使用直接口服抗凝剂存在风险。这些药物相互作用的临床影响尚未在临床试验中得到研究。本研究旨在评估药物相互作用对静脉血栓栓塞复发和出血的影响。
这是一项回顾性队列研究,纳入了接受阿哌沙班或利伐沙班联合抗肿瘤治疗的静脉血栓栓塞癌症患者。通过比较有药物相互作用的患者与无药物相互作用的患者的药物相互作用对静脉血栓栓塞复发和出血率的影响来确定药物相互作用的影响。
主要复合终点(静脉血栓栓塞复发和出血事件)分别发生在药物相互作用组的 65%和非药物相互作用组的 62%。抗有丝分裂微管抑制剂与更高的静脉血栓栓塞复发和轻微出血事件发生率相关,而激素治疗和烷化剂与更高的轻微出血事件发生率相关。在药物相互作用组中,与中度至重度药物相互作用相比,轻度药物相互作用时报告的主要出血事件较少。与利伐沙班相比,阿哌沙班的静脉血栓栓塞复发时间无差异。
由于样本量小,我们的研究结果无法证实药物相互作用会增加出血或静脉血栓栓塞复发的风险。需要进一步的前瞻性研究,但临床医生应意识到这些药物相互作用,并使用现有文献进行识别。