Akl Elie A, Vasireddi Srinivasa Rao, Gunukula Sameer, Barba Maddalena, Sperati Francesca, Terrenato Irene, Muti Paola, 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):CD006649. doi: 10.1002/14651858.CD006649.pub4.
Compared to patients without cancer, patients with cancer who receive anticoagulant treatment for venous thromboembolism are more likely to develop recurrent venous thromboembolism (VTE).
To compare the efficacy and safety of three types of parenteral anticoagulants for the initial treatment of VTE in patients with cancer.
A comprehensive search for studies of anticoagulation in cancer patients including a February 2010 electronic search of: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ISI Web of Science.
Randomized clinical trials (RCTs) comparing low molecular weight heparin (LMWH), unfractionated heparin (UFH), and fondaparinux in patients with cancer and objectively confirmed VTE.
Using a standardized data form, data was extracted in duplicate on methodological quality, participants, interventions, and outcomes of interest that included mortality, recurrent VTE, major bleeding, minor bleeding, postphlebitic syndrome, quality of life, and thrombocytopenia.
Of 3986 identified citations, 16 RCTs were eligible: 13 compared LMWH to UFH, two compared fondaparinux to heparin, and one compared dalteparin to tinzaparin. Meta-analysis of 11 studies showed a statistically significant reduction in mortality at three months of follow up with LMWH compared with UFH (relative risk (RR) 0.71; 95% confidence interval (CI) 0.52 to 0.98). There was little change in the effect estimate after excluding studies of lower methodological quality (RR 0.72; 95% CI 0.52 to 1.00). A meta-analysis of three studies comparing LMWH with UFH showed no statistically significant reduction in VTE recurrence (RR 0.78; 95% CI 0.29 to 2.08). The overall quality of evidence was low for LMWH versus UFH due to imprecision and likely publication bias. There were no statistically significant differences between heparin and fondaparinux for the outcomes of death (RR 1.27; 95% CI 0.88 to 1.84), recurrent VTE (RR 0.95; 95% CI 0.57 to 1.60), major bleeding (RR 0.79; 95% CI 0.39 to1.63) or minor bleeding (RR 1.50; 95% CI 0.87 to 2.59). The one study comparing dalteparin to tinzaparin did not find a statistically significant difference in mortality (RR 0.86; 95% CI 0.43 to 1.73).
AUTHORS' CONCLUSIONS: LMWH is possibly superior to UFH in the initial treatment of VTE in patients with cancer. Additional trials focusing on patient important outcomes will further inform the questions addressed in this review.
与未患癌症的患者相比,因静脉血栓栓塞接受抗凝治疗的癌症患者更易发生复发性静脉血栓栓塞(VTE)。
比较三种胃肠外抗凝剂对癌症患者VTE初始治疗的疗效和安全性。
全面检索癌症患者抗凝治疗的研究,包括2010年2月对以下数据库的电子检索:Cochrane对照试验中央注册库(CENTRAL)、MEDLINE、EMBASE和ISI科学网。
比较低分子量肝素(LMWH)、普通肝素(UFH)和磺达肝癸钠在经客观确诊VTE的癌症患者中的随机临床试验(RCT)。
使用标准化数据表格,对方法学质量、参与者、干预措施及感兴趣的结局(包括死亡率、复发性VTE、大出血、小出血、血栓形成后综合征、生活质量和血小板减少症)进行重复数据提取。
在3986条检索到的文献中,16项RCT符合要求:13项比较LMWH与UFH,2项比较磺达肝癸钠与肝素,1项比较达肝素与替扎肝素。11项研究的荟萃分析显示,与UFH相比,LMWH在随访3个月时死亡率有统计学显著降低(相对危险度(RR)0.71;95%置信区间(CI)0.52至0.98)。排除方法学质量较低的研究后,效应估计值变化不大(RR 0.72;95%CI 0.52至1.00)。三项比较LMWH与UFH的研究的荟萃分析显示,VTE复发率无统计学显著降低(RR 0.78;95%CI 0.29至2.08)。由于结果不精确且可能存在发表偏倚,LMWH与UFH对比的总体证据质量较低。肝素与磺达肝癸钠在死亡(RR 1.27;95%CI 0.88至1.84)、复发性VTE(RR 0.95;95%CI 0.57至1.60)、大出血(RR 0.79;95%CI 0.39至1.63)或小出血(RR 1.50;95%CI 0.87至2.59)结局方面无统计学显著差异。一项比较达肝素与替扎肝素的研究未发现死亡率有统计学显著差异(RR 0.86;95%CI 0.43至1.73)。
在癌症患者VTE的初始治疗中,LMWH可能优于UFH。关注患者重要结局的更多试验将为本次综述中涉及的问题提供进一步信息。