Biological Hematology Department, Hôpital TENON APHP Hôpitaux Universitaires de l'Est Parisien, INSERM UMRS 938 Université Pierre et Marie Curie, Paris 6, Paris, France.
Internal Medicine Department, Hôpital Louis Mourier, APHP, Colombes, France.
J Thromb Haemost. 2017 May;15(5):848-857. doi: 10.1111/jth.13659. Epub 2017 Mar 21.
Patients with cancer-associated thrombosis (CAT) carry a higher risk of recurrence, bleeding and mortality as compared with non-cancer patients. The specific profiles of cancer patients, combining frequent co-morbidities, the use of anti-tumoral therapies and the cancer progression itself, represent a major therapeutic challenge for choosing a long-term anticoagulant treatment. This review discusses the practical basis of making a choice between the available drugs for a long-term antithrombotic strategy, linked to their pharmacology, mechanism of action, evidence of clinical benefits, and advantages and limitations in such a complex clinical context. In patients with cancer, low-molecular-weight heparins (LMWHs) are the preferred option for the secondary prevention of venous thromboembolism according to current guidelines, because their efficacy is significantly superior to vitamin K antagonists (VKAs). Even though LMWHs are effective and safe in cancer patients, they require daily subcutaneous injections, which may be problematic for a long-term therapy that may exceed 6 months' duration. Compared with VKAs, non-vitamin-K antagonist oral anticoagulants or direct oral anticoagulants (DOACs) are more target specific and do not require laboratory monitoring, whereas the oral route of administration makes them potentially attractive alternatives to LMWH. In randomized controlled trials in the general population DOACs have been shown to be non-inferior to VKAs in terms of efficacy with a lower rate of clinically relevant or major bleeding. However, given the limited number of cancer patients enrolled in these studies (with poorly defined active cancer), available trials are inconclusive regarding the usefulness of DOACs in the cancer setting. Ongoing head-to-head comparisons vs. LMWH in patients with CAT may allow an informed choice to be made regarding the DOAC option.
与非癌症患者相比,癌症相关血栓形成(CAT)患者的复发、出血和死亡风险更高。癌症患者的特定情况,包括经常合并的多种疾病、抗肿瘤治疗的使用以及癌症的进展本身,为选择长期抗凝治疗带来了重大的治疗挑战。这篇综述讨论了在现有药物中进行选择的实际基础,用于制定长期抗血栓策略,这些药物与它们的药理学、作用机制、临床获益证据以及在这种复杂临床环境中的优缺点有关。根据当前指南,对于静脉血栓栓塞症的二级预防,低分子肝素(LMWH)是癌症患者的首选,因为其疗效明显优于维生素 K 拮抗剂(VKA)。尽管 LMWH 在癌症患者中有效且安全,但它们需要每天皮下注射,这在可能超过 6 个月的长期治疗中可能会出现问题。与 VKAs 相比,非维生素 K 拮抗剂口服抗凝剂或直接口服抗凝剂(DOACs)更具靶向性,不需要实验室监测,而口服给药途径使它们成为 LMWH 的潜在有吸引力的替代品。在一般人群的随机对照试验中,DOAC 在疗效方面不劣于 VKA,且临床相关或大出血的发生率较低。然而,鉴于这些研究中纳入的癌症患者数量有限(癌症处于活动状态的定义不明确),可用的试验对于 DOAC 在癌症患者中的作用尚无定论。正在进行的 CAT 患者与 LMWH 的头对头比较可能有助于在 DOAC 选择方面做出明智的决策。