Di Nisio Marcello, Porreca Ettore, Ferrante Noemi, Otten Hans-Martin, Cuccurullo Franco, Rutjes Anne W S
Department of Medicine and Aging; Centre for Aging Sciences (Ce.S.I.), Internal Medicine Unit, “University G. D’Annunzio”Foundation, Chieti, Italy.
Cochrane Database Syst Rev. 2012 Feb 15(2):CD008500. doi: 10.1002/14651858.CD008500.pub2.
Venous thromboembolism (VTE) often complicates the clinical course of cancer disease. The risk is further increased by chemotherapy but the safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain.
To assess the efficacy and safety of primary thromboprophylaxis in ambulatory cancer patients receiving chemotherapy.
The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched 3 May 2011) and CENTRAL (2011, Issue 2). The authors searched clinical trials registries and reference lists of relevant studies.
Randomised controlled trials (RCTs) comparing unfractionated heparin (UFH), low molecular weight heparin (LMWH), vitamin K antagonists (VKA), direct thrombin inhibitors, direct factor Xa inhibitors or mechanical intervention to no intervention or placebo; or comparing two different anticoagulants.
Data were extracted on methodological quality, patients, interventions and outcomes including symptomatic VTE and major bleeding as the primary effectiveness and safety outcomes, respectively.
Nine RCTs with a total of 3538 patients were considered. None of the RCTs tested UFH, fondaparinux, direct factor Xa inhibitors or mechanical interventions. Overall, the risk of bias was low in most of the studies. LMWH, when compared with inactive control, significantly reduced the incidence of symptomatic VTE (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.41 to 0.93) with no evidence of heterogeneity (I(2) = 0%). The number needed to treat to prevent a symptomatic VTE was 60. LMWH was associated with a 60% increase in major bleeding when compared with inactive control, although this was not statistically significant (RR 1.57, 95% CI 0.69 to 3.60; I(2) = 10%). There was a 45% reduction in overall VTE (RR 0.55, 95% CI 0.34 to 0.88; I(2) = 0%) while for symptomatic pulmonary embolism, asymptomatic VTE, minor bleeding and one-year mortality the differences between the LMWH and control groups were not statistically significant. The effect of the vitamin K antagonist warfarin on preventing symptomatic VTE, measured in only one study, was not statistically significant (RR 0.15, 95% CI 0.02 to 1.20). In one RCT of patients with myeloma, LMWH was associated with a 67% reduction in symptomatic VTE (RR 0.33, 95% CI 0.14 to 0.83) compared with warfarin, with no differences in major bleeding. Antithrombin, evaluated in one study on paediatric patients, had no significant effect on VTE nor major bleeding when compared with inactive control.
AUTHORS' CONCLUSIONS: Primary thromboprophylaxis with LMWH significantly reduced the incidence of symptomatic VTE in ambulatory cancer patients treated with chemotherapy. However, the lack of power hampers definite conclusions on the effects on major safety outcomes, which mandates additional studies to determine the risk to benefit ratio of LMWH in this setting.
静脉血栓栓塞症(VTE)常使癌症患者的临床病程复杂化。化疗会进一步增加该风险,但对于接受化疗的癌症患者进行一级血栓预防的安全性和有效性尚不确定。
评估门诊接受化疗的癌症患者进行一级血栓预防的有效性和安全性。
Cochrane外周血管疾病小组检索了其专业注册库(最后检索时间为2011年5月3日)和Cochrane系统评价数据库(2011年第2期)。作者还检索了临床试验注册库以及相关研究的参考文献列表。
随机对照试验(RCT),比较普通肝素(UFH)、低分子肝素(LMWH)、维生素K拮抗剂(VKA)、直接凝血酶抑制剂、直接Xa因子抑制剂或机械干预与不干预或安慰剂;或比较两种不同的抗凝剂。
提取了有关方法学质量、患者、干预措施和结局的数据,包括有症状的VTE和大出血,分别作为主要有效性和安全性结局。
共纳入9项RCT,涉及3538例患者。没有RCT对UFH、磺达肝癸钠、直接Xa因子抑制剂或机械干预进行检验。总体而言,大多数研究的偏倚风险较低。与无活性对照相比,LMWH显著降低了有症状VTE的发生率(风险比(RR)0.62,95%置信区间(CI)0.41至0.93),且无异质性证据(I² = 0%)。预防一例有症状VTE所需治疗人数为60。与无活性对照相比,LMWH使大出血增加60%,尽管这无统计学意义(RR 1.57,95% CI 0.69至3.60;I² = 10%)。总体VTE减少了45%(RR 0.55,95% CI 0.34至0.88;I² = 0%),而对于有症状的肺栓塞、无症状VTE、轻微出血和一年死亡率,LMWH组与对照组之间的差异无统计学意义。仅在一项研究中测量的维生素K拮抗剂华法林预防有症状VTE的效果无统计学意义(RR 0.15,95% CI 0.02至1.20)。在一项针对骨髓瘤患者的RCT中,与华法林相比,LMWH使有症状VTE减少67%(RR 0.33,95% CI 0.14至0.83),大出血方面无差异。在一项针对儿科患者的研究中评估的抗凝血酶,与无活性对照相比,对VTE和大出血均无显著影响。
对于接受化疗的门诊癌症患者,采用LMWH进行一级血栓预防可显著降低有症状VTE的发生率。然而,由于研究效能不足,妨碍了就其对主要安全性结局的影响得出明确结论,这就需要开展更多研究以确定在此情况下LMWH的风险效益比。