Akl Elie A, Gunukula Sameer, Barba Maddalena, Yosuico Victor E D, van Doormaal Frederiek F, Kuipers Saskia, Middeldorp Saskia, Dickinson Heather O, Bryant Andrew, Schünemann Holger
Department of Medicine, State University of New York at Buffalo, ECMC CC-142, 462 Grider Street, Buffalo, NY, USA, 14215.
Cochrane Database Syst Rev. 2011 Apr 13(4):CD006652. doi: 10.1002/14651858.CD006652.pub3.
Anticoagulation may improve survival in patients with cancer through an antitumor effect in addition to the perceived antithrombotic effect.
To evaluate the efficacy and safety of parenteral anticoagulants in patients with cancer with no therapeutic or prophylactic indication for anticoagulation.
A comprehensive search included (1) an electronic search (February 2010) of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL) Issue 1, 2010, MEDLINE, EMBASE and ISI the Web of Science; (2) handsearch of conference proceedings; (3) checking of references of included studies; and (4) use of the 'related citation' feature in PubMed.
Randomized controlled trials (RCTs) assessing the benefits and harms of parenteral anticoagulation in patients with cancer but no therapeutic or prophylactic indication for anticoagulation.
Using a standardized form we extracted in duplicate data on methodological quality, participants, interventions and outcomes of interest including all-cause mortality, symptomatic thromboembolism, major bleeding, minor bleeding and quality of life (QoL).
Of 8187 identified citations, nine RCTs enrolling 2857 patients fulfilled the inclusion criteria. In all included RCTs the intervention consisted of heparin (either unfractionated heparin or low molecular weight heparin). Overall, the effect of heparin therapy on mortality was not statistically significant at 12 months (risk ratio (RR) 0.93; 95% CI 0.85 to 1.02) but it was statistically significant at 24 months (RR 0.92; 95% CI 0.88 to 0.97). Heparin therapy was associated with a statistically and clinically important reduction in venous thromboembolism (RR 0.55; 95% CI 0.37 to 0.82). There were no statistically significant effects on major bleeding (RR 1.30; 95% CI 0.59 to 2.88), minor bleeding (RR 1.05; 95% 0.75 to 1.46) or QoL. The quality of evidence was high for symptomatic venous thromboembolism, moderate for mortality, major bleeding and minor bleeding, and low for QoL.
AUTHORS' CONCLUSIONS: Heparin was associated with a significant reduction of death at 24 months but not 12 months. It was also associated with a reduction in venous thromboembolism but based on the RCTs in this review it had no significant effect on major bleeding, minor bleeding or QoL. Future research should further investigate the survival benefit of different types of anticoagulants in patients with different types and stages of cancer. The decision for a patient with cancer to start heparin therapy for survival benefit should balance the benefits and downsides and integrate the patient's values and preferences.
抗凝治疗除了具有公认的抗血栓形成作用外，还可能通过抗肿瘤作用提高癌症患者的生存率。
评估在无抗凝治疗或预防指征的癌症患者中，胃肠外抗凝剂的疗效和安全性。
全面检索包括：（1）2010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）2010年第1期、MEDLINE、EMBASE和ISI科学网；（2）手工检索会议论文集；（3）检查纳入研究的参考文献；（4）使用PubMed中的“相关引用”功能。
评估胃肠外抗凝剂对癌症患者的益处和危害，但患者无抗凝治疗或预防指征的随机对照试验（RCT）。
我们使用标准化表格，一式两份提取关于方法学质量、参与者、干预措施和感兴趣结局的数据，包括全因死亡率、症状性血栓栓塞、大出血、小出血和生活质量（QoL）。
在8187条检索到的文献中，9项纳入2857例患者的RCT符合纳入标准。在所有纳入的RCT中，干预措施均为肝素（普通肝素或低分子肝素）。总体而言，肝素治疗对12个月死亡率的影响无统计学意义（风险比（RR）0.93；95%CI 0.85至1.02），但在24个月时有统计学意义（RR 0.92；95%CI 0.88至0.97）。肝素治疗与静脉血栓栓塞的统计学及临床显著降低相关（RR 0.55；95%CI 0.37至0.82）。对大出血（RR 1.30；95%CI 0.59至2.88）、小出血（RR 1.05；95%CI 0.75至1.46）或生活质量无统计学显著影响。症状性静脉血栓栓塞的证据质量高，死亡率、大出血和小出血的证据质量中等，生活质量的证据质量低。
肝素与24个月时死亡显著降低相关，但12个月时无此关联。它还与静脉血栓栓塞减少相关，但基于本综述中的RCT，对大出血、小出血或生活质量无显著影响。未来研究应进一步调查不同类型抗凝剂对不同类型和分期癌症患者的生存获益情况。癌症患者为生存获益开始肝素治疗的决策应权衡利弊，并综合考虑患者的价值观和偏好。
