Bauersachs Rupert, Khorana Alok A, Lee Agnes Y Y, Soff Gerald
Department of Vascular Medicine Klinikum Darmstadt GmbH Darmstadt Germany.
Center of Thrombosis and Hemostasis University of Mainz Mainz Germany.
Res Pract Thromb Haemost. 2020 Apr 4;4(4):532-549. doi: 10.1002/rth2.12327. eCollection 2020 May.
Cancer-associated venous thromboembolism (VTE) is a frequent, potentially life-threatening event that complicates cancer management. Anticoagulants are the cornerstone of therapy for the treatment and prevention of cancer-associated thrombosis (CAT); factor Xa-inhibiting direct oral anticoagulants (DOACs; apixaban, edoxaban, and rivaroxaban), which have long been recommended for the treatment of VTE in patients without cancer, have been investigated in this setting. The first randomized comparisons of DOACs against low-molecular-weight heparin for the treatment of CAT indicated that DOACs are efficacious in this setting, with findings reflected in recent updates to published guidance on CAT treatment. However, the higher risk of bleeding events (particularly in the gastrointestinal tract) with DOACs highlights the need for appropriate patient selection. Further insights will be gained from additional studies that are ongoing or awaiting publication. The efficacy and safety of DOAC thromboprophylaxis in ambulatory patients with cancer at a high risk of VTE have also been assessed in placebo-controlled randomized controlled trials of apixaban and rivaroxaban. Both studies showed efficacy benefits with DOACs, but both studies also showed a nonsignificant increase in major bleeding events while on treatment. This review summarizes the evidence base for rivaroxaban use in CAT, the patient profile potentially most suited to DOAC use, and ongoing controversies under investigation. We also describe ongoing studies from the CALLISTO (Cancer Associated thrombosis-expLoring soLutions for patients through Treatment and Prevention with RivarOxaban) program, which comprises several randomized clinical trials and real-world evidence studies, including investigator-initiated research.
癌症相关静脉血栓栓塞（VTE）是一种常见的、可能危及生命的事件，会使癌症治疗变得复杂。抗凝剂是治疗和预防癌症相关血栓形成（CAT）的基石；长期以来推荐用于非癌症患者VTE治疗的Xa因子抑制直接口服抗凝剂（DOACs；阿哌沙班、依度沙班和利伐沙班）已在这种情况下进行了研究。DOACs与低分子肝素治疗CAT的首次随机对照试验表明，DOACs在这种情况下是有效的，这些发现反映在最近更新的CAT治疗指南中。然而，DOACs出血事件风险较高（尤其是在胃肠道）凸显了进行适当患者选择的必要性。正在进行或等待发表的其他研究将带来更多见解。阿哌沙班和利伐沙班的安慰剂对照随机对照试验也评估了DOACs在VTE高风险门诊癌症患者中进行血栓预防的疗效和安全性。两项研究均显示DOACs有疗效益处，但两项研究也均显示治疗期间主要出血事件有非显著性增加。本综述总结了利伐沙班用于CAT的证据基础、可能最适合使用DOACs的患者特征以及正在研究的争议问题。我们还描述了CALLISTO（通过利伐沙班治疗和预防探索癌症相关血栓形成患者的解决方案）项目正在进行的研究，该项目包括多项随机临床试验和真实世界证据研究，包括研究者发起的研究。
