华法林对比安慰剂和肝素预防肿瘤患者CVCs相关血栓有效性和安全性的系统评价

Systematic review on the efficacy and safety of warfarin compared with placebo and heparin for the prevention of central venous catheters-associated thrombosis in patients with cancer

目的:通过对华法林预防肿瘤患者中心静脉导管(Central venous catheters,CVCs)相关血栓的随机对照试验和(或)临床对照试验文献进行Meta分析,系统评价华法林预防肿瘤患者CVCs相关血栓的有效性和安全性,为临床肿瘤患者CVCs相关血栓的预防提供理论依据。方法:检索MEDLINE、OVID、EBSCO、EMBASE、中国生物医学文献数据库(CBM)、中国知网(CNKI),同时辅以引文检索和手工检索,获取基本数据。对符合纳入标准的随机对照试验和(或)临床对照试验文献进行方法学质量评价和数据资料提取,采用RevMan5.0.25统计软件进行Meta分析。结果:共纳入7篇随机对照试验和临床对照试验文献,其中有关华法林和安慰剂比较的有6篇文献(共计1 522例肿瘤患者),有关华法林和肝素比较的有1篇文献(包括45例肿瘤患者)。系统评价结果显示:1.华法林和安慰剂比较,两组CVCs相关血栓发生率差异具有统计学意义(RR=0.68,95%CI[0.52,0.89];P=0.004);2组出血发生率和死亡率差异都无统计学意义,出血发生率(RR=2.12,95%CI[0.82,5.48];P=0.12),死亡率(RR=1.01,95%CI[0.58,1.74];P=0.98)。2.华法林与肝素相比,两组CVCs相关血栓发生率、出血发生率、死亡率差异均没有统计学意义,CVCs相关血栓发生率(RR=0.58,95%CI[0.19,1.79];P=0.35),出血发生率(RR=0.29,95%CI[0.01,6.84];P=0.45),死亡率(RR=0.58,95%CI[0.19,1.79];P=0.35)。结论:华法林和安慰剂比较,预防肿瘤患者CVCs相关血栓有一定的有效性和安全性,华法林能有效降低肿瘤患者CVCs相关血栓的发生率,并且不增加出血发生率和死亡率;华法林和肝素相比,在预防肿瘤患者CVCs相关血栓有效性和安全性方面作用相当。但是由于相关研究较少,尚需更多设计严格的大样本的随机对照试验以进一步增加证据的强度。

Objective：To evaluate the efficacy and safety of warfarin for the prevention of central venous catheters-associated（CVCs associated） thrombosis in patients with cancer systematically via a meta-analysis of randomized controlled trials and（or） clinical controlled trials on warfarin for the prevention of CVCs associated thrombosis in patients with cancer,and to provide theoretical basis for the clinical prevention of CVCs associated thrombosis in patients with cancer.Methods：Databases including MEDLINE,OVID,EBSCO,EMBASE,CBM and CNKI were searched,and at the same time,reference retrieval and manual searching were used to acquire basic data.For the literatures which met the inclusion criteria,methodology quality assessment was performed and data information was extracted.A meta-analysis was done by RevMan 5.0.25 statistical software.Results：Seven randomized controlled trials and clinical controlled trials were included.There were six literatures（including 1 522 patients with cancer） about warfarin vs.placebo and one literature（including 45 cancer patients） about warfarin vs.heparin.The results of systematic review were showed as follows：1.In Warfarin vs.placebo,the difference of CVCs associated thrombosis incidence had statistical significance between the two groups（RR=0.68,95%CI[0.52,0.89];P=0.004）.However,the difference of bleeding incidence and mortality rate had no statistical significance,with bleeding incidence（RR=2.12,95%CI[0.82,5.48];P=0.12） and mortality rate（RR=1.01,95%CI[0.58,1.74];P=0.98）.2.In Warfarin vs.heparin,the difference of CVCs-associated thrombosis incidence,bleeding incidence and mortality rate had no statistical significance,with the incidence of CVCs associated thrombosis（RR=0.58,95%CI[0.19,1.79];P=0.35）,bleeding incidence（RR=0.29,95%CI[0.01,6.84];P=0.45）,and mortality rate（RR=0.58,95%CI[0.19,1.79];P=0.35）.Conclusion：Warfarin,compared with placebo,is effective and safe in the prevention of CVCs associated thrombosis in patients with cancer.Warfarin can decrease CVCs associated thrombosis incidence of patients with cancer effectively and does not increase bleeding incidence or mortality rate.In Warfarin vs.heparin,the efficacy and safety are equal in the prevention of CVCs associated thrombosis in patients with cancer.But because of scanty related studies,more randomized controlled trials with strict design and large samples are still needed to further raise the intensity of proof.