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[2020年直接口服抗凝剂在癌症相关血栓形成管理中的作用]

[The role of direct oral anticoagulants in the management of cancer-associated thrombosis in 2020].

作者信息

Auditeau Claire, Talbot Alexis, Blandinières Adeline, Smadja David M, Gendron Nicolas

机构信息

AP-HP, université de Paris, Hôpital Necker-Enfants Malades, laboratoire d'hématologie, Paris, France.

AP-HP, université de Paris, Hôpital Saint-Louis, service d'immuno-hématologie clinique, 75010 Paris, France.

出版信息

Bull Cancer. 2020 May;107(5):574-585. doi: 10.1016/j.bulcan.2020.02.010. Epub 2020 Apr 3.

Abstract

Direct oral anticoagulants, anti-IIa or anti-Xa, are widely used in the treatment and prevention of venous thromboembolic disease as well as in nonvalvular atrial fibrillation. Direct oral anticoagulants are characterized by a rapid onset of activity, a predictable response and a relatively wide therapeutic window. Nevertheless, theoretical drug interactions exist since direct oral anticoagulants are substrates of the transport protein P-glycoprotein and/or of isoforms of cytochromes P450 pathway. Direct oral anticoagulants do not have a marketing authorization for the treatment of cancer-associated thrombosis unlike low-molecular-weight heparins which remain the gold standard treatment today. However, recent studies have compared low-molecular-weight heparins to direct oral anticoagulants in the treatment of cancer-associated thrombosis. Results of these studies showed a non-inferiority of direct oral anticoagulants in the prevention of recurrent thromboembolic events but at the cost of an increased hemorrhagic risk, in particular for patients with gastrointestinal and urogenital cancers. Thus, international guidelines, unlike French guidelines, integrate them in first line of the therapeutic strategy of cancer patients. We are certainly entering an era of personalized therapy for cancer-associated thrombosis, considering cancer type and also the theoretical risk of drug interactions with anti-cancer treatments or supportive care.

摘要

直接口服抗凝剂,即抗凝血酶IIa或抗凝血因子Xa药物,广泛应用于静脉血栓栓塞性疾病的治疗和预防以及非瓣膜性心房颤动的治疗。直接口服抗凝剂的特点是起效迅速、反应可预测且治疗窗相对较宽。然而,由于直接口服抗凝剂是转运蛋白P-糖蛋白和/或细胞色素P450途径同工型的底物,因此存在理论上的药物相互作用。与仍是当今金标准治疗药物的低分子肝素不同,直接口服抗凝剂没有用于治疗癌症相关血栓形成的上市许可。然而,最近的研究比较了低分子肝素与直接口服抗凝剂在治疗癌症相关血栓形成方面的效果。这些研究结果显示,直接口服抗凝剂在预防复发性血栓栓塞事件方面并不逊色,但代价是出血风险增加,尤其是对于胃肠道和泌尿生殖系统癌症患者。因此,与法国指南不同,国际指南将其纳入癌症患者治疗策略的一线用药。考虑到癌症类型以及与抗癌治疗或支持性护理药物相互作用的理论风险,我们无疑正在进入一个针对癌症相关血栓形成的个性化治疗时代。

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