抗凝药防治急性静脉血栓栓塞症的有效性和安全性的系统评价和网状Meta分析
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摘要
目的系统评价新型抗凝口服药(NOACs)和传统抗凝药防治急性静脉血栓栓塞症(VTE)的有效性和安全性。方法系统检索2018-03-10之前Pub Med、Em Base、Cochrane Library等数据库,纳入NOACs防治急性VTE的随机对照试验(RCT)共12篇,涉及患者42343例(试验组21162例,对照组21181例),进行数据提取和质量评价后,用R软件和Stata软件进行直接比较和网状Meta分析。结果 NOACs与传统抗凝药物的有效性相比,总静脉血栓与相关死亡事件的发生率差异无统计学意义(均P> 0. 05)。安全性:阿哌沙班组(10 mg bid)与阿哌沙班组(2. 5 mg bid)、利伐沙班组(10 mg od)、利伐沙班组(15 mg bid)和标准治疗组(2. 0≤INR≤3. 0)这4组相比,重大出血及临床相关非重大出血事件的发生率显著降低,差异均有统计学意义(均P <0. 05)。达比加群酯组(150 mg bid)、依度沙班组(30 or 60 mg qd)与华法林组(2. 0≤INR≤3. 0)相比,重大出血及临床相关非重大出血事件的发生率显著降低,差异均有统计学意义(均P <0. 05)。结论 NOACs防治急性VTE的有效性具有和传统抗凝药物同样的效果,且NOACs的安全性优于标准治疗和华法林。
Objective To evaluate the efficacy and safety of novel oral anticoagulants( NOACs) and traditional anticoagulants for the prevention and treatment of acute venous thromboembolism( VTE). Methods PubMed,EmBase,Cochrane Library,and other databases were systematically searched up to March 10,2018. Randomized controlled trials( RCT) for the prevention and treatment of acute VTE by the inclusion of NOACs were selected. Totally of 12 trials were included. The 42343 cases were included in this study,including 21162 cases accepted NOACs( treatment group),other 21181 cases accepted other drugs( control group). The direct comparison and the network meta-analysis were carried out by using R and Stata software after data extraction and quality evaluation. Results In terms of efficacy,there was no significant difference in the incidence of total venous thrombosis and related deaths between the NOACs and traditional anticoagulants( all P > 0. 05). In terms of safety,apixaban group( 10 mg bid) compared with apixaban group( 2. 5 mg bid),rivaroxaban group( 10 mg od),rivaroxaban group( 15 mg bid),and standard treatment group( 2. 0 ≤INR≤3. 0) respectively,the incidence of major bleeding and clinically relevant non-major bleeding was lower,the difference were significant( all P < 0. 05). The incidence of major bleeding and clinically relevant non-major bleeding in dabigatran( 150 mg bid) group and edoxaban( 30 or 60 mg qd) group was lower than that in the warfarin group( 2. 0 ≤INR≤3. 0),the difference were significantly( all P < 0. 05). Conclusion The NOACs has the same effect as traditional anticoagulants in the prevention and treatment of acute VTE. In terms of safety,the NOACs is superior to standard therapy and warfarin.
Objective To evaluate the efficacy and safety of novel oral anticoagulants( NOACs) and traditional anticoagulants for the prevention and treatment of acute venous thromboembolism( VTE). Methods PubMed,EmBase,Cochrane Library,and other databases were systematically searched up to March 10,2018. Randomized controlled trials( RCT) for the prevention and treatment of acute VTE by the inclusion of NOACs were selected. Totally of 12 trials were included. The 42343 cases were included in this study,including 21162 cases accepted NOACs( treatment group),other 21181 cases accepted other drugs( control group). The direct comparison and the network meta-analysis were carried out by using R and Stata software after data extraction and quality evaluation. Results In terms of efficacy,there was no significant difference in the incidence of total venous thrombosis and related deaths between the NOACs and traditional anticoagulants( all P > 0. 05). In terms of safety,apixaban group( 10 mg bid) compared with apixaban group( 2. 5 mg bid),rivaroxaban group( 10 mg od),rivaroxaban group( 15 mg bid),and standard treatment group( 2. 0 ≤INR≤3. 0) respectively,the incidence of major bleeding and clinically relevant non-major bleeding was lower,the difference were significant( all P < 0. 05). The incidence of major bleeding and clinically relevant non-major bleeding in dabigatran( 150 mg bid) group and edoxaban( 30 or 60 mg qd) group was lower than that in the warfarin group( 2. 0 ≤INR≤3. 0),the difference were significantly( all P < 0. 05). Conclusion The NOACs has the same effect as traditional anticoagulants in the prevention and treatment of acute VTE. In terms of safety,the NOACs is superior to standard therapy and warfarin.
引文
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[7]张超,董圣杰,曾宪涛.R软件gemtc程序包在网状Meta分析中的应用[J].中国循证医学杂志,2013,13(10):1258-1264.
[8]张天嵩.Stata软件network组命令在网状Meta分析中的应用[J].中国循证医学杂志,2015,15(11):1352-1356.
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[11]RUPERT B,SCOTT D B,BENJAMIN B,et al.Oral rivaroxaban for symptomatic venous thromboembolism[J].New Eng J Med,2010,363(26):2499-2510.
[12]丁宇,徐昆,司全金,等.利伐沙班预防高龄老年血栓性疾病的有效性和安全性研究[J].中国循环杂志,2017,8(32):788-791.
[13]BLLER H,PRINS M,LENSIN A,et al.Oral rivaroxaban for the treatment of symptomatic pulmonary embolism[J].New Eng J Med,2012,366(14):1287-1297.
[14]WESTENDORF J B,SCHELLONG S,GERLACH H,et al.Prevention of thromboembolic complications in patients with superficial-vein thrombosis given rivaroxaban or fondaparinux:the open-label,randomised,non-inferiority SURPRISE phase 3b trial[J].Lancet Haematol,2017,3026(17):105-113.
[15]COHEN A,SPIRO T B,LLER H,et al.Rivaroxaban for thromboprophylaxis in acutely ill medical patients[J].New Eng J Med,2013,368(6):513-523.
[16]AGNELLI G,BULLER H R,COHEN A,et al.Oral apixaban for the treatment of acute venous thromboembolism[J].New Eng JMed,2013,369(9):799-808.
[17]GOLDHABER S,LEIZOROVICZ A,KAKKAR A,et al.Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients[J].New Eng J Med,2011,365(23):2167-2177.
[18]NAKAMURA M,NISHIKAWA M,KOMURO I,et al.Apixaban for the treatment of Japanese subjects with acute venous thromboembolism(Amplify-J study)[J].Circ J,2015,79(6):1230-1236.
[19]LLER H B,DCOUSUS H,GROSSO M,et al.Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism[J].New Eng J Med,2013,369(15):1406-1415.
[20]HISATAKE S,KABUKI T,KIUCHI S,et al.Short-term subcutaneous fondaparinux and oral edoxaban for acute venous thromboembolism[J].Circ J,2017,81(6):855-861.
[21]DI MINNO M N D,AGENO W,LUPOLI R,et al.Direct oral anticoagulants for the treatment of acute venous thromboembolism in patients with cancer:a meta-analysis of randomised controlled trials[J].Eur Respirat J,2017,50(3):1-5.
[22]HULLE T,KOOIMAN J,EXTER P L,et al.Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism:a systematic review and meta‐analysis[J].J Thrombosis Haemostasis,2014,12(3):320-328.
[23]FOX B D,KAHN S R,LANGLEBEN D,et al.Efficacy and safety of novel oral anticoagulants for treatment of acute venous thromboembolism:direct and adjusted indirect meta-analysis of randomised controlled trials[J].Br Med J,2012,345(7498):1-10.
[24]孙虎,张莹,叶远征,等.口服新型凝血酶抑制剂与维生素K拮抗剂比较治疗急性静脉血栓栓塞的系统评价和Meta分析[J].中国循证心血管医学杂志,2017,9(1):14-18.
[25]GOMEZ-OUTES A,TERLEIRA-FERNANDEZ A I,LECUM-BERRI R,et al.Direct oral anticoagulants in the treatment of acute venous thromboembolism:a systematic review and meta-analysis[J].Thromb Res,2014,134(4):774-782.
[26]易跃雄,张蔚,刘小媛,等.网状Meta分析图形结果解读[J].中国循证医学杂志,2015,15(1):103-109.
[2]TAPSON V F.Advances in the diagnosis and treatment of acute pulmonary embolism[J].F1000 Med Reports,2012,4(9):1-11.
[3]汪志超,方宏.新型口服抗凝药防治急性静脉血栓栓塞症的研究进展[J].实用心脑肺血管病杂志,2017,25(9):7-12.
[4]STREIFF M B,AGNELLI G,CONNORS J M,et al.Guidance for the treatment of deep vein thrombosis and pulmonary embolism[J].J Thrombosis Thrombolysis,2016,41(16):32-67.
[5]蒋文瀚,陈炳为,郑建光,等.R语言meta包在Meta分析中的应用[J].循证医学,2011,11(5):305-309.
[6]汪徐林,秦正积,陆益花,等.Stata软件在网状Meta分析中的应用[J].现代预防医学,2016,43(19):3461-3464,3482.
[7]张超,董圣杰,曾宪涛.R软件gemtc程序包在网状Meta分析中的应用[J].中国循证医学杂志,2013,13(10):1258-1264.
[8]张天嵩.Stata软件network组命令在网状Meta分析中的应用[J].中国循证医学杂志,2015,15(11):1352-1356.
[9]SCHULMAN S,KAKKAR A K,GOLDHABER S Z,et al.Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis[J].Circulation,2014,129(7):764-772.
[10]SCHULMAN S,KEARON C,KAKKAR A,et al.Dabigatran versus warfarin in the treatment of acute venous thromboembolism[J].New Eng J Med,2009,361(24):2342-2352.
[11]RUPERT B,SCOTT D B,BENJAMIN B,et al.Oral rivaroxaban for symptomatic venous thromboembolism[J].New Eng J Med,2010,363(26):2499-2510.
[12]丁宇,徐昆,司全金,等.利伐沙班预防高龄老年血栓性疾病的有效性和安全性研究[J].中国循环杂志,2017,8(32):788-791.
[13]BLLER H,PRINS M,LENSIN A,et al.Oral rivaroxaban for the treatment of symptomatic pulmonary embolism[J].New Eng J Med,2012,366(14):1287-1297.
[14]WESTENDORF J B,SCHELLONG S,GERLACH H,et al.Prevention of thromboembolic complications in patients with superficial-vein thrombosis given rivaroxaban or fondaparinux:the open-label,randomised,non-inferiority SURPRISE phase 3b trial[J].Lancet Haematol,2017,3026(17):105-113.
[15]COHEN A,SPIRO T B,LLER H,et al.Rivaroxaban for thromboprophylaxis in acutely ill medical patients[J].New Eng J Med,2013,368(6):513-523.
[16]AGNELLI G,BULLER H R,COHEN A,et al.Oral apixaban for the treatment of acute venous thromboembolism[J].New Eng JMed,2013,369(9):799-808.
[17]GOLDHABER S,LEIZOROVICZ A,KAKKAR A,et al.Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients[J].New Eng J Med,2011,365(23):2167-2177.
[18]NAKAMURA M,NISHIKAWA M,KOMURO I,et al.Apixaban for the treatment of Japanese subjects with acute venous thromboembolism(Amplify-J study)[J].Circ J,2015,79(6):1230-1236.
[19]LLER H B,DCOUSUS H,GROSSO M,et al.Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism[J].New Eng J Med,2013,369(15):1406-1415.
[20]HISATAKE S,KABUKI T,KIUCHI S,et al.Short-term subcutaneous fondaparinux and oral edoxaban for acute venous thromboembolism[J].Circ J,2017,81(6):855-861.
[21]DI MINNO M N D,AGENO W,LUPOLI R,et al.Direct oral anticoagulants for the treatment of acute venous thromboembolism in patients with cancer:a meta-analysis of randomised controlled trials[J].Eur Respirat J,2017,50(3):1-5.
[22]HULLE T,KOOIMAN J,EXTER P L,et al.Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism:a systematic review and meta‐analysis[J].J Thrombosis Haemostasis,2014,12(3):320-328.
[23]FOX B D,KAHN S R,LANGLEBEN D,et al.Efficacy and safety of novel oral anticoagulants for treatment of acute venous thromboembolism:direct and adjusted indirect meta-analysis of randomised controlled trials[J].Br Med J,2012,345(7498):1-10.
[24]孙虎,张莹,叶远征,等.口服新型凝血酶抑制剂与维生素K拮抗剂比较治疗急性静脉血栓栓塞的系统评价和Meta分析[J].中国循证心血管医学杂志,2017,9(1):14-18.
[25]GOMEZ-OUTES A,TERLEIRA-FERNANDEZ A I,LECUM-BERRI R,et al.Direct oral anticoagulants in the treatment of acute venous thromboembolism:a systematic review and meta-analysis[J].Thromb Res,2014,134(4):774-782.
[26]易跃雄,张蔚,刘小媛,等.网状Meta分析图形结果解读[J].中国循证医学杂志,2015,15(1):103-109.