Akl Elie A, Kahale Lara, Terrenato Irene, Neumann Ignacio, Yosuico Victor E D, Barba Maddalena, Sperati Francesca, Schünemann Holger
Department of Internal Medicine, American University of Beirut, Riad El Solh St, Beirut, Lebanon.
Cochrane Database Syst Rev. 2014 Jun 4(6):CD006466. doi: 10.1002/14651858.CD006466.pub4.
Several basic research and clinical studies have led to the hypothesis that oral anticoagulants may improve the survival of patients with cancer through an antitumor effect in addition to their antithrombotic effect.
To evaluate the efficacy and safety of oral anticoagulants in patients with cancer with no therapeutic or prophylactic indication for anticoagulation.
We performed a comprehensive search for studies of anticoagulation in patients with cancer including 1. a February 2013 electronic search of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE; 2. a handsearch of the American Society of Clinical Oncology (starting with its first volume, 1982) and of the American Society of Hematology (starting with the 2003 issue); 3. checking of references of included studies; 4. use of the 'related citation' feature in PubMed; and 5. searching clinical trials.gov for ongoing studies.
Randomized controlled trials (RCTs) comparing vitamin K antagonist or other oral anticoagulants with no intervention or placebo in patients with cancer without clinical evidence of venous thromboembolism.
Using a standardized data form, we extracted data on risk of bias, participants, interventions and outcomes of interest that included all-cause mortality, venous thromboembolism, major bleeding, and minor bleeding.
Of 9559 identified citations, seven RCTs (eight reports) fulfilled the inclusion criteria. The oral anticoagulant was warfarin in six of these RCTs and apixaban in the seventh RCT. The comparator was either placebo or no intervention. The use of warfarin had no effect on mortality at six months (risk ratio (RR) 0.98; 95% confidence interval (CI) 0.82 to 1.22), one year (RR 0.97; 95% CI 0.89 to 1.04), two years (RR 0.98; 95% CI 0.81 to 1.18), or five years (RR 0.92; 95% CI 0.83 to 1.01). One study assessed the effect of warfarin on venous thromboembolism and did not show or exclude a beneficial or detrimental of effect (RR 0.15; 95% CI 0.02 to 1.20). Warfarin increased both major bleeding (RR 4.24; 95% CI 1.86 to 9.65) and minor bleeding (RR 3.19; 95% CI 1.83 to 5.55). We judged the quality of evidence as moderate for all outcomes.The study assessing the effect of apixaban did not show or exclude a beneficial effect or detrimental of apixaban on mortality at six months (RR 0.16; 95% CI 0.01 to 1.66); major bleeding (RR 0.62; 95% CI 0.06 to 6.63); and minor bleeding (RR 2.87; 95% CI 0.16 to 51.82). We judged the quality of evidence as low for all outcomes.
AUTHORS' CONCLUSIONS: Existing evidence does not suggest a mortality benefit from oral anticoagulation in patients with cancer while the risk for bleeding is increased.
多项基础研究和临床研究提出了这样的假设，即口服抗凝剂除具有抗血栓形成作用外，还可能通过抗肿瘤作用提高癌症患者的生存率。
评估口服抗凝剂在无抗凝治疗或预防指征的癌症患者中的疗效和安全性。
我们全面检索了有关癌症患者抗凝治疗的研究，包括：1. 2013年2月对以下数据库进行电子检索：Cochrane对照试验中心注册库（CENTRAL）、医学期刊数据库（MEDLINE）和荷兰医学文摘数据库（EMBASE）；2. 手工检索美国临床肿瘤学会（从其第一卷，即1982年开始）和美国血液学会（从2003年刊开始）的文献；3. 检查纳入研究的参考文献；4. 使用PubMed中的“相关引文”功能；5. 在临床试验注册库（clinical trials.gov）中搜索正在进行的研究。
比较维生素K拮抗剂或其他口服抗凝剂与无干预措施或安慰剂对无静脉血栓栓塞临床证据的癌症患者影响的随机对照试验（RCT）。
我们使用标准化数据表格，提取了关于偏倚风险、参与者、干预措施和感兴趣结局的数据，这些结局包括全因死亡率、静脉血栓栓塞、大出血和小出血。
在9559条检索到的文献中，7项RCT（8篇报告）符合纳入标准。这些RCT中有6项使用的口服抗凝剂是华法林，第7项使用的是阿哌沙班。对照措施为安慰剂或无干预措施。使用华法林对6个月时的死亡率无影响（风险比（RR）0.98；95%置信区间（CI）0.82至1.22）、1年时（RR 0.97；95%CI 0.89至1.04）、2年时（RR 0.98；95%CI 0.81至1.18）或5年时（RR 0.92；95%CI 0.83至1.01）。一项研究评估了华法林对静脉血栓栓塞的影响，未显示或排除其有益或有害作用（RR 0.15；95%CI 0.02至1.20）。华法林增加了大出血（RR 4.24；95%CI 1.86至9.65）和小出血（RR 3.19；95%CI 1.83至5.55）的发生率。我们判定所有结局的证据质量为中等。评估阿哌沙班影响的研究未显示或排除阿哌沙班对6个月时死亡率的有益或有害作用（RR 0.16；95%CI 0.01至1.66）；大出血（RR 0.62；95%CI 0.06至6.63）；以及小出血（RR 2.87；95%CI 0.16至51.82）。我们判定所有结局的证据质量为低等。
现有证据未表明口服抗凝治疗能使癌症患者受益于降低死亡率，同时出血风险却增加了。
