Carrier Marc, Cameron Chris, Delluc Aurélien, Castellucci Lana, Khorana Alok A, Lee Agnes Y Y
Department of Medicine, The Ottawa Hospital Research Institute, University of Ottawa, Ontario Canada.
Thromb Res. 2014 Dec;134(6):1214-9. doi: 10.1016/j.thromres.2014.09.039. Epub 2014 Oct 8.
Current clinical practice guidelines all recommend the use of therapeutic doses of low molecular weight heparins (LMWH) for the initial and long-term treatment of cancer-related thrombosis. The use of vitamin-K antagonists (VKA) is acceptable if LMWH is not available. Direct oral anticoagulants (DOACs) have been shown to be comparable to conventional therapy for the acute treatment of VTE but their efficacy and safety in cancer patients remains uncertain.
A systematic literature search strategy was conducted using MEDLINE, EMBASE, and the EBM reviews. Randomized controlled trials (RCTs) reporting rates of recurrent VTE and major bleeding in cancer patients were included. Relative risks (RR) (95% confidence intervals (CI)) for these outcomes were generated.
A total of 9 RCTs (2310 patients) were included in our analysis. In comparison to VKA, LMWH showed a significant reduction in recurrent VTE events (RR: 0.52; 95% CI: 0.36 to 0.74) whereas DOACs did not (RR: 0.66; 95% CI: 0.39 to 1.11). LMWH was associated with a non significant increase in the risk of major bleeding (RR: 1.06; 95% CI: 0.5 to 2.23) whereas DOACs showed a non significant reduction (RR: 0.78; 95% CI: 0.42 to 1.44). Annualized risks of recurrent VTE and major bleeding among patients randomized to VKA were higher in the LMWH studies as compared to the studies assessing DOACs suggesting that a higher risk cancer population were enrolled in the LMWH studies.
LMWH should be used for the treatment of acute cancer-associated thrombosis. The use DOACs cannot be supported until trials comparing them to LMWH are conducted.
当前临床实践指南均推荐使用治疗剂量的低分子肝素(LMWH)进行癌症相关血栓形成的初始和长期治疗。若无法获得LMWH,使用维生素K拮抗剂(VKA)也是可以接受的。直接口服抗凝剂(DOACs)已被证明在急性治疗静脉血栓栓塞(VTE)方面与传统疗法相当,但其在癌症患者中的疗效和安全性仍不确定。
采用MEDLINE、EMBASE和循证医学综述进行系统的文献检索策略。纳入报告癌症患者复发性VTE和大出血发生率的随机对照试验(RCT)。生成这些结果的相对风险(RR)(95%置信区间(CI))。
我们的分析共纳入9项RCT(2310例患者)。与VKA相比,LMWH显示复发性VTE事件显著减少(RR:0.52;95%CI:0.36至0.74),而DOACs则未显示(RR:0.66;95%CI:0.39至1.11)。LMWH与大出血风险的非显著增加相关(RR:1.06;95%CI:0.5至2.23),而DOACs则显示非显著降低(RR:0.78;95%CI:0.42至1.44)。与评估DOACs的研究相比,LMWH研究中随机分配至VKA的患者复发性VTE和大出血的年化风险更高,这表明LMWH研究纳入了风险更高的癌症患者群体。
LMWH应用于治疗急性癌症相关血栓形成。在进行将DOACs与LMWH进行比较的试验之前,无法支持使用DOACs。