Akl Elie A, Ramly Elie P, Kahale Lara A, Yosuico Victor E D, Barba Maddalena, Sperati Francesca, Cook Deborah, Schünemann Holger
Department of Internal Medicine, American University of Beirut, Riad El Solh St, Beirut, Lebanon.
Cochrane Database Syst Rev. 2014 Oct 15(10):CD006468. doi: 10.1002/14651858.CD006468.pub5.
Central venous catheter (CVC) placement increases the risk of thrombosis in people with cancer. Thrombosis often necessitates the removal of the CVC, resulting in treatment delays and thrombosis-related morbidity and mortality.
To evaluate the relative efficacy and safety of anticoagulation for thromboprophylaxis in people with cancer with a CVC.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 12, 2012), MEDLINE Ovid (January 1966 to February 2013), and EMBASE Ovid (1980 to February 2013). We handsearched conference proceedings, checked references of included studies, used the 'related citations' feature within PubMed, and searched clinicaltrials.gov for ongoing studies.
Randomized controlled trials (RCTs) comparing the effects of any dose of unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), vitamin K antagonists (VKA), or fondaparinux with no intervention or placebo or comparing the effects of two different anticoagulants in people with cancer and a CVC.
Teams of two review authors independently used a standardized form to extract data in duplicate. They resolved any disagreements by discussion. They extracted data on risk of bias, participants, interventions, and outcomes. Outcomes of interest included mortality, symptomatic deep venous thrombosis (DVT), asymptomatic DVT, major bleeding, minor bleeding, infection, and thrombocytopenia. Where possible, we conducted meta-analyses using the random-effects model.
Of 9559 identified citations, we included 12 RCTs (17 publications) reporting follow-up data on 2823 participants. Two of the RCTs included children. Of the 10 RCTs including 2564 adults, one compared prophylactic dose heparin with low-dose VKA. Three RCTs compared VKA with no VKA and four RCTs compared heparin with no heparin. Two additional trials had three separate arms comparing heparin, VKA, and no intervention. Prophylactic-dose heparin, compared with no heparin, was associated with a statistically significant reduction in symptomatic DVT (risk ratio (RR) 0.48; 95% confidence interval (CI) 0.27 to 0.86; moderate-quality evidence). However, results did not confirm or exclude a beneficial or detrimental effect of heparin on mortality (RR 0.82; 95% CI 0.53 to 1.26; moderate-quality evidence), major bleeding (RR 0.49; 95% CI 0.03 to 7.84; low-quality evidence), infection (RR 1.00; 95% CI 0.54 to 1.85; moderate-quality evidence); thrombocytopenia (RR 1.03; 95% CI 0.80 to 1.33; moderate-quality evidence), or minor bleeding (RR 1.35; 95% CI: 0.62 to 2.92). Low-dose VKAs, compared with no VKAs, were associated with a statistically significant reduction in asymptomatic DVT (RR 0.43; 95% CI 0.30 to 0.62). Results did not confirm or exclude a beneficial or detrimental effect of VKAs on mortality (RR 1.04; 95% CI 0.89 to 1.22; low-quality evidence), symptomatic DVT (RR 0.51; 95% CI 0.21 to 1.22; low-quality evidence), major bleeding (RR 7.60; 95% CI 0.94 to 61.49; very-low-quality evidence), or minor bleeding (RR 3.14; 95% CI 0.14 to 71.51). The use of heparin, compared with VKA was associated with a statistically significant increase in thrombocytopenia (RR 3.73; 95% CI 2.26 to 6.16; low-quality evidence) and asymptomatic DVT (RR 1.74; 95% CI 1.20 to 2.52). However, results did not show or exclude a beneficial or detrimental effect on any of the other outcomes of interest (very-low-quality evidence).
AUTHORS' CONCLUSIONS: Compared with no anticoagulation, we found a statistically significant reduction of symptomatic DVT with heparin and asymptomatic DVT with VKA. Heparin was associated with a higher risk of thrombocytopenia and asymptomatic DVT when compared with VKA. However, the findings did not rule out other clinically important benefits and harms. People with cancer with CVCs considering anticoagulation should balance the possible benefit of reduced thromboembolic complications with the possible harms and burden of anticoagulants.
中心静脉导管（CVC）置入会增加癌症患者发生血栓形成的风险。血栓形成常常需要拔除CVC，从而导致治疗延误以及与血栓形成相关的发病和死亡。
评估抗凝治疗在预防癌症患者CVC相关血栓形成方面的相对疗效和安全性。
我们检索了Cochrane对照试验中心注册库（CENTRAL，2012年第12期）、MEDLINE Ovid数据库（1966年1月至2013年2月）以及EMBASE Ovid数据库（1980年至2013年2月）。我们手工检索了会议论文集，检查纳入研究的参考文献，利用PubMed中的“相关引文”功能，并在clinicaltrials.gov上检索正在进行的研究。
随机对照试验（RCT），比较任何剂量的普通肝素（UFH）、低分子肝素（LMWH）、维生素K拮抗剂（VKA）或磺达肝癸钠与不干预或安慰剂的效果，或者比较两种不同抗凝剂在癌症合并CVC患者中的效果。
由两名综述作者组成的小组独立使用标准化表格一式两份提取数据。他们通过讨论解决任何分歧。他们提取了关于偏倚风险、参与者、干预措施和结局的数据。感兴趣的结局包括死亡率、有症状的深静脉血栓形成（DVT）、无症状DVT、大出血、小出血、感染和血小板减少症。在可能的情况下，我们使用随机效应模型进行荟萃分析。
在9559条检索到的引文中，我们纳入了12项RCT（17篇出版物），报告了2823名参与者的随访数据。其中两项RCT纳入了儿童。在纳入2564名成年人的10项RCT中，一项比较了预防性剂量肝素与低剂量VKA。三项RCT比较了VKA与不使用VKA，四项RCT比较了肝素与不使用肝素。另外两项试验有三个独立的组，分别比较肝素、VKA和不干预。与不使用肝素相比，预防性剂量肝素与有症状DVT的统计学显著降低相关（风险比（RR）0.48；95%置信区间（CI）0.27至0.86；中等质量证据）。然而，结果未证实或排除肝素对死亡率（RR 0.82；95% CI 0.53至1.26；中等质量证据）、大出血（RR 0.49；95% CI 0.03至7.84；低质量证据）、感染（RR 1.00；95% CI 0.54至1.85；中等质量证据）、血小板减少症（RR 1.03；95% CI 0.80至1.33；中等质量证据）或小出血（RR 1.35；95% CI：0.62至2.92）的有益或有害影响。与不使用VKA相比，低剂量VKA与无症状DVT的统计学显著降低相关（RR 0.43；95% CI 0.30至0.62）。结果未证实或排除VKA对死亡率（RR 1.04；95% CI 0.89至1.22；低质量证据）、有症状DVT（RR 0.51；95% CI 0.21至1.22；低质量证据）、大出血（RR 7.60；95% CI 0.94至61.49；极低质量证据）或小出血（RR 3.14；95% CI 0.14至71.51）的有益或有害影响。与VKA相比，使用肝素与血小板减少症（RR 3.73；95% CI 2.26至6.16；低质量证据）和无症状DVT（RR 1.74；95% CI 1.20至2.52）的统计学显著增加相关。然而，结果未显示或排除对任何其他感兴趣结局的有益或有害影响（极低质量证据）。
与不进行抗凝相比，我们发现肝素可使有症状DVT以及VKA可使无症状DVT出现统计学显著降低。与VKA相比，肝素与血小板减少症和无症状DVT的较高风险相关。然而，这些发现并未排除其他临床上重要的益处和危害。考虑进行抗凝治疗的癌症合并CVC患者应权衡减少血栓栓塞并发症的可能益处与抗凝剂可能带来的危害和负担。
