中药注射液联合低分子肝素预防骨科术后深静脉血栓形成的网状Meta分析

Network Meta-analysis of traditional Chinese medicine injection combined with low molecular weight heparin in prevention of deep venous thrombosis after orthopaedic surgery

目的采用网状Meta分析评价中药注射液联合低分子肝素(lowmolecularweightheparin,LMWH)预防骨科术后深静脉血栓(deep venous thrombosis,DVT)形成的有效性和安全性,以及对患者凝血功能和术后出血量的影响,旨在为临床用药提供循证参考。方法计算机检索Cochrane Library、Embase、Pub Med、Web of Science、中国知网、万方、维普等数据库,收集中药注射液联合LMWH对比单纯LMWH预防骨科术后DVT形成的随机对照试验(randomized controlled trial,RCT),检索时限为建库至2020年12月31日。由2位研究者独立筛选文献、提取数据,并根据Cochrane的偏倚风险评估工具对纳入文献进行质量评价,运用R软件进行网状Meta分析。结果共纳入57项RCT,包含5024例患者,涉及13种中药(丹参川芎嗪、丹参多酚酸盐、银杏达莫、红花黄色素、疏血通、血栓通、血塞通、丹红、丹参、七叶皂苷钠、苦碟子、脉络宁、红花)注射液。网状Meta分析结果显示,与LMWH单纯治疗相比,除血塞通外,其余12种中药注射液联合LMWH均可有效预防DVT形成,排序前3的中药注射液是疏血通(72.2%)>红花黄色素(70.9%)>丹参川芎嗪(66.1%);在降低D-二聚体(D-dimer,DD)水平方面,排序前3的中药注射液是丹红(82.7%)>丹参川芎嗪(76.0%)>苦碟子(74.4%);在降低纤维蛋白原(fibrinogen,FIB)水平方面,排序前3的中药注射液是丹参川芎嗪(92.0%)>银杏达莫(87.0%)>疏血通(57.8%);在延长凝血酶原时间(prothrombin time,PT)方面,排序前3的中药注射液是丹红(85.7%)>红花黄色素(68.3%)>血栓通(68.0%);在延长活化部分凝血活酶时间(activated partial thromboplastin time,APTT)方面,排序前3的中药注射液是七叶皂苷钠(100.0%)>丹红(84.5%)>红花(66.0%);在减少术后出血量方面,疏血通联合LMWH明显优于银杏达莫联合LMWH,排序前3的中药注射液是疏血通(94.5%)>丹参川芎嗪(58.5%)>血栓通(57.9%);在减少不良反应发生方面,排序前3的中药注射液是疏血通(86.3%)>红花黄色素(79.5%)>丹参川芎嗪(66.5%)。结论与LMWH单纯治疗相比,疏血通、红花黄色素、丹参川芎嗪联合LMWH预防DVT形成的疗效较佳,丹参川芎嗪联合LMWH降低DD的疗效较佳,丹参川芎嗪、银杏达莫联合LMWH降低FIB的疗效较佳,红花黄色素联合LMWH延长PT的疗效较佳,七叶皂苷钠、丹红联合LMWH延长APTT的疗效较佳,疏血通、红花黄色素联合LMWH减少不良反应的效果较佳,纳入的13种中药注射液与LMWH联合均不会增加术后出血量,比较安全。可能以红花黄色素、丹参川芎嗪联合LMWH预防骨科术后DVT形成的疗效为最佳,值得临床推荐使用。

Objective To evaluate the efficacy and safety of traditional Chinese medicine injection combined with low molecular weight heparin(LMWH) in preventing formation of deep venous thrombosis(DVT) after orthopedic surgery and its effect on blood coagulation function and postoperative blood loss in patients by network Meta-analysis, in order to provide evidence-based reference for clinical medication. Methods The databases of Cochrane Library, Embase, Pub Med, Web of Science, Sino Med, China knowledge network, Wanfang and VIP were searched by computer. And the randomized controlled trial(RCT) which traditional Chinese medicine injection combined with LMWH compares with LMWH alone to prevent the formation of DVT after orthopedic surgery, limited from the database to December 31, 2020, was collected. After screening the literature, two researchers independently screened the literature, extracted the data and evaluated the quality of the included literature according to the bias risk assessment tool of Cochrane, and used R software for network Meta-analysis. Results A total of 5024 patients and 13 kinds of traditional Chinese medicine injection [Salvia Miltiorrhiza Ligustrazine(丹参川芎嗪), Salvia Miltiorrhiza Polyphenolates(丹参多酚酸盐), Ginkgo Biloba Dipyridamole(银杏达莫), Safflower Yellow(红花黄色素), Shuxuetong(疏血通), Xueshuantong(血栓通), Xuesaitong(血塞通), Danhong(丹红), Salvia Miltiorrhiza(丹参), Sodium Aescin(七叶皂苷钠), Ixeris Sonchifolia(苦碟子), Mailuoning(脉络宁), Safflower(红花)] with 57 items of RCT were included. The results of network Meta-analysis showed that: Compared with the simple treatment of LMWH, except Xueshuantong, the other 12 kinds of traditional Chinese medicine injection combined with LMWH can effectively prevent the formation of DVT. The top three were combined Shuxuetong(72.2%), Safflower Yellow(70.9%), Salvia Miltiorrhiza Ligustrazine(66.1%) with LMWH, respectively. In terms of reducing the level of D-dimer(DD), the top three were Danhong(82.7%) and Salviae Miltiorrhizae Ligustrazineand(76.%), Ixeris Sonchifolia(74.4%) combined with LMWH, respectively. In terms of lowering fibrinogen(Fib) levels, the top three were Salviae Miltiorrhizae Ligustrazine(92%), Ginkgo Biloba Dipyridamole(87.0%) and Shuxuetong(57.8%) combined with LMWH, respectively. In terms of prolonging prothrombin time(PT), the top three were Danhong(85.7%), safflower yellow(68.3%) and Xueshuantong(68.0%) combined with LMWH, respectively. In terms of prolonging the activated partial thromboplastin time(APTT), the top three were Sodium Aescin(100.0%), Danhong(84.5%) and Safflower(66.0%) combined with LMWH, respectively. In terms of reducing postoperative blood loss, Shuxuetong combined with LMWH was significantly better than Ginkgo biloba and Dipyridamole combined with LMWH. The top three were Shuxuetong(94.5%), Salviae Miltiorrhizae Ligustrazine(58.5%), Xueshuantong(57.9%) combined with LMWH. In terms of reducing the occurrence of adverse reactions, the top three were Shuxuetong(86.3%), Safflower yellow(79.5%) and Salviae Miltiorrhizae Ligustrazine(66.5%) combined with LMWH. Conclusion Compared with LMWH alone, Shuxuetong, Safflower Yellow, Salvia Miltiorrhiza Ligustrazine combined with LMWH were more effective in preventing the formation of DVT. Salvia Miltiorrhiza Ligustrazine combined with LMWH were more effective in reducing DD. Salvia Miltiorrhiza Ligustrazine and Ginkgo Biloba combined with LMWH was better in reducing FIB. Safflower Yellow combined with LMWH was better in prolonging PT, and Sodium Aescin and Danhong combined with LMWH were better in prolonging APTT. Shuxuetong, safflower yellow combined with LMWH was more effective in reducing adverse reactions. The combination of 13 kinds of traditional Chinese medicine injection and LMWH will not increase the amount of postoperative bleeding, so it is relatively safe. To sum up, Safflower Yellow, Salvia Miltiorrhiza Ligustrazine combined with LMWH are the best, which should be recommended by clinical pharmacists.