不同类型房颤患者使用新型口服抗凝药物和华法林预防卒中的疗效比较:Meta分析
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摘要
目的比较新型口服抗凝药物(NOACs)与华法林预防不同类型心房颤动(房颤)患者卒中的有效性和安全性。方法应用计算机从PubMed、 Cochrane图书馆、 Elsevier、 Web of Science、中国知网、万方等电子数据库中检索自建库至2018年7月关于口服抗凝治疗预防房颤患者卒中的随机对照临床试验(RCTs)。获取数据资料后用RevMan 5.3和STATA软件进行荟萃及偏倚统计分析,比较口服抗凝治疗在阵发性房颤与持续性或永久性房颤患者卒中预防的有效性和安全性。结果通过筛选最终纳入了4项大型Ⅲ期RCTs,对其荟萃分析表明在阵发性房颤患者中,无论使用NOACs还是华法林,患者卒中和全身性栓塞发生率[NOACs组(2.58%, 197/7 642) vs.华法林组(3.25%, 193/5 929), RR=0.83, 95%CI:0.61～1.13, P=0.24, I2=57%]和大出血发生率[NOACs组(6.4%, 489/7 642) vs.华法林组(7.12%, 422/5 929),RR=0.88, 95%CI:0.78～1.00, P=0.06, I2=0%]无显著差异。在持续性或永久性房颤患者中,NOACs组卒中和全身性栓塞发生率显著低于华法林组[NOACs组(3.22%, 813/25 197) vs.华法林组(7.12%, 846/20 956), RR=0.82, 95%CI:0.75～0.90, P <0.000 1, I2=0%],同时大出血事件也显著降低[NOACs组(5.5%, 1 386/25 197) vs.华法林组(6.45%, 1 351/20 956), RR=0.85, 95%CI:0.73～0.99, P=0.03, I~2=77%]。结论阵发性房颤患者使用NOACs预防卒中的有效性和安全性与华法林相当,持续性或永久性房颤患者使用NOACs预防卒中的有效性和安全性较华法林好。
AIM To evaluate the efficacy and safety of new oral anticoagulants (NOACs) in patients with various atrial fibrillation( AF) patterns compared with warfarin. METHODS Comprehensive literatures searches were conducted using the PubMed, Cochrane Library, Elsevier, Web of Science, CNKI and Wanfang from inception to July 2018. Randomized controlled trials (RCTs) focusing on efficacy and safety of oral anticoagulant therapy for prevention of stroke in patients with AF were adopted. Statistical analyses were performed using RevMan 5.3 and STATA software. RESULTS Four phase Ⅲ RCTs were finally appraised and included. In patients with paroxysmal AF, NOACs was comparable to warfarin for stroke and systemic embolism (NOACs group (2.58%, 197/7 642) vs. warfarin group (3.25%, 193/5 929), RR = 0.83, 95%CI: 0.61-1.13, P = 0.24, I2= 57%) as well as major bleeding (NOACs group (6.4%, 489/7 642) vs. warfarin group (7.12%, 422/5 929), RR = 0.88, 95%CI: 0.78-1.00, P = 0.06, I2= 0%). In patients with persistent or permanent AF, NOACs had a favorable point estimate in stroke and systemic embolism(NOACs group (3.22%,813/25 197) vs. warfarin group (7.12%, 846/20 956), RR = 0.82, 95%CI: 0.75-0.90, P < 0.000 1, I2=0%) as well as major bleeding(NOACs group (5.5%, 1 386/25 197) vs. warfarin group (6.45%, 1 351/20 956), RR = 0.85, 95% CI: 0.73-0.99, P = 0.03, I2= 77%) compared with warfarin. CONCLUSION NOACs were similarly effective and safe for the prevention of stroke in patients with paroxysmal AF but more effective and safer in those with persistent or permanent AF compared with warfarin.
AIM To evaluate the efficacy and safety of new oral anticoagulants (NOACs) in patients with various atrial fibrillation( AF) patterns compared with warfarin. METHODS Comprehensive literatures searches were conducted using the PubMed, Cochrane Library, Elsevier, Web of Science, CNKI and Wanfang from inception to July 2018. Randomized controlled trials (RCTs) focusing on efficacy and safety of oral anticoagulant therapy for prevention of stroke in patients with AF were adopted. Statistical analyses were performed using RevMan 5.3 and STATA software. RESULTS Four phase Ⅲ RCTs were finally appraised and included. In patients with paroxysmal AF, NOACs was comparable to warfarin for stroke and systemic embolism (NOACs group (2.58%, 197/7 642) vs. warfarin group (3.25%, 193/5 929), RR = 0.83, 95%CI: 0.61-1.13, P = 0.24, I2= 57%) as well as major bleeding (NOACs group (6.4%, 489/7 642) vs. warfarin group (7.12%, 422/5 929), RR = 0.88, 95%CI: 0.78-1.00, P = 0.06, I2= 0%). In patients with persistent or permanent AF, NOACs had a favorable point estimate in stroke and systemic embolism(NOACs group (3.22%,813/25 197) vs. warfarin group (7.12%, 846/20 956), RR = 0.82, 95%CI: 0.75-0.90, P < 0.000 1, I2=0%) as well as major bleeding(NOACs group (5.5%, 1 386/25 197) vs. warfarin group (6.45%, 1 351/20 956), RR = 0.85, 95% CI: 0.73-0.99, P = 0.03, I2= 77%) compared with warfarin. CONCLUSION NOACs were similarly effective and safe for the prevention of stroke in patients with paroxysmal AF but more effective and safer in those with persistent or permanent AF compared with warfarin.
引文
[1]JANUARY CT,WANN LS,ALPERT JS,et al.2014 AHAACC/HRS guideline for the management of patients with atrial fibrillation:a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society[J].J Am Coll Cardiol,2014,64(21):e1-e76.
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[4]BANERJEE A,TAILLANDIER S,OLESEN JB,et al.Pattern of atrial fibrillation and risk of outcomes:the Loire Valley Atrial Fibrillation Project[J].Int J Cardiol,2013,167(6):2682-2687.
[5]NIEUWLAAT R,DINH T,OLSSON SB,et al.Should we abandon the common practice of withholding oral anticoagulation in paroxysmal atrial fibrillation?[J].Eur Heart J,2008,29(7):915-922.
[6]黄从新,张澍,黄德嘉,等.心房颤动:目前的认识和治疗建议-2015[J].中国心脏起搏与心电生理杂志,2015,29(5):377-434.
[7]中华医学会心血管病学分会,中国老年学学会心脑血管病专业委员会.华法林抗凝治疗的中国专家共识[J].中华内科杂志,2013,52(1):76-82.
[8]CONNOLLY SJ,EZEKOWITZ MD,YUSUF S,et al.Dabigatran versus warfarin in patients with atrial fibrillation[J].N Engl JMed,2009,361(12):1139-1151.
[9]GOMEZ-OUTES A,TERLEIRA-FERNANDEZ AI,CALVO-ROJAS G,et al.Dabigatran,rivaroxaban,or apixaban versus warfarin in patients with nonvalvular atrial fibrillation:a systematic review and meta-analysis of subgroups[J].Thrombosis,2013,2013:640723.
[10]XIONG Q,LAU YC,SENOO K,et al.Non-vitamin K antagonist oral anticoagulants (NOACs) in patients with concomitant atrial fibrillation and heart failure:a systemic review and metaanalysis of randomized trials[J].Eur J Heart Fail,2015,17(11):1192-1200.
[11]LARSEN TB,NIELSEN PB,SKJOTH F,et al.Non-vitamin Kantagonist oral anticoagulants and the treatment of venous thromboembolism in cancer patients:a semi systematic review and meta-analysis of safety and efficacy outcomes[J].PLoS One,2014,9(12):e114445.
[12]KIM IS,KIM HJ,KIM TH,et al.Non-vitamin K antagonist oral anticoagulants have better efficacy and equivalent safety compared to warfarin in elderly patients with atrial fibrillation:a systematic review and meta-analysis[J].J Cardiol,2018,72(2):105-112.
[13]NIELSEN PB,LANE DA,RASMUSSEN LH,et al.Renal function and non-vitamin K oral anticoagulants in comparison with warfarin on safety and efficacy outcomes in atrial fibrillation patients:a systemic review and meta-regression analysis[J].Clin Res Cardiol,2015,104(5):418-429.
[14]SENOO K,LAU YC,DZESHKA M,et al.Efficacy and safety of non-vitamin K antagonist oral anticoagulants vs.warfarin in Japanese patients with atrial fibrillation-meta-analysis[J].Circ J,2015,79(2):339-345.
[15]BEGG CB,MAZUMDAR M.Operating characteristics of a rank correlation test for publication bias[J].Biometrics,1994,50(4):1088-1101.
[16]EGGER M,DAVEY SMITH G,SCHNEIDER M,et al.Bias in meta-analysis detected by a simple,graphical test[J].BMJ,1997,315(7109):629-634.
[17]FLAKER G,EZEKOWITZ M,YUSUF S,et al.Efficacy and safety of dabigatran compared to warfarin in patients with paroxysmal,persistent,and permanent atrial fibrillation:results from the RE-LY(Randomized Evaluation of Long-Term Anticoagulation Therapy)study[J].J Am Coll Cardiol,2012,59(9):854-855.
[18]AL-KHATIB SM,THOMAS L,WALLENTIN L,et al.Outcomes of apixaban vs.warfarin by type and duration of atrial fibrillation:results from the ARISTOTLE trial[J].Eur Heart J,2013,34(31):2464-2471.
[19]STEINBERG BA,HELLKAMP AS,LOKHNYGINA Y,et al Higher risk of death and stroke in patients with persistent vs.paroxysmal atrial fibrillation:results from the ROCKET-AF tria[J].Eur Heart J,2015,36(5):288-296.
[20]LINK MS,GIUGLIANO RP,RUFF CT,et al.Stroke and mortality risk in patients with various patterns of atrial fibrillation:results from the ENGAGE AF-TIMI 48 trial(effective anticoagulation with factor Xa next generation in atrial fibrillation-thrombolysis in myocardial infarction 48)[J].Circ Arrhythm Electrophysiol,2017,10(1):e004267.
[21]PANCHOLY SB,SHARMA PS,PANCHOLY DS,et al.Metaanalysis of gender differences in residual stroke risk and major bleeding in patients with nonvalvular atrial fibrillation treated with oral anticoagulants[J].Am J Cardiol,2014,113(3):485-490.
[22]KAMATH S,CHIN BS,BLANN AD,et al.A study of platelet activation in paroxysmal,persistent and permanent atrial fibrillation[J].Blood Coagul Fibrinolysis,2002,13(7):627-636.
[23]DONG Y,DONG Q.New oral anticoagulants:how do we use them wisely?[J].Curr Cardiol Rep,2015,17(9):626.
[24]VOUKALIS C,LIP GY,SHANTSILA E.Drug-drug interactions of non-vitamin K oral anticoagulants[J].Expert Opin Drug Metab Toxicol,2016,12(12):1445-1461.
[25]张卫芳,鲍慧慧,熊爱珍,等.新型口服抗凝药与抗逆转录病毒药物的相互作用[J].药品评价,2018,15(10):12-15.
[26]冯瑞江,鮑慧慧,熊爱珍,等.新型口服抗凝药与抗癫痫药物的相互作用[J].中国新药与临床杂志,2018,37(8):443-447.
[27]张卫芳,陆社桂,熊淑华,等.达比加群酯联合塞来昔布致上消化道出血1例[J].中国新药与临床杂志,2016,35(8):596-598.
[28]侯微,房德敏,钱皎,等.房颤合并肝硬化患者的口服抗凝药物选择及抗栓策略研究[J].中国现代应用药学,2018,35(10):1549-1553.
[2]PETERSEN P.Thromboembolic complications in atrial fibrillation[J].Stroke,1990,21(1):4-13.
[3]HART RG,PEARCE LA,ROTHBART RM,et al.Stroke with intermittent atrial fibrillation:incidence and predictors during aspirin therapy.Stroke Prevention in Atrial Fibrillation Investigators[J].J Am Coll Cardiol,2000,35(1):183-187.
[4]BANERJEE A,TAILLANDIER S,OLESEN JB,et al.Pattern of atrial fibrillation and risk of outcomes:the Loire Valley Atrial Fibrillation Project[J].Int J Cardiol,2013,167(6):2682-2687.
[5]NIEUWLAAT R,DINH T,OLSSON SB,et al.Should we abandon the common practice of withholding oral anticoagulation in paroxysmal atrial fibrillation?[J].Eur Heart J,2008,29(7):915-922.
[6]黄从新,张澍,黄德嘉,等.心房颤动:目前的认识和治疗建议-2015[J].中国心脏起搏与心电生理杂志,2015,29(5):377-434.
[7]中华医学会心血管病学分会,中国老年学学会心脑血管病专业委员会.华法林抗凝治疗的中国专家共识[J].中华内科杂志,2013,52(1):76-82.
[8]CONNOLLY SJ,EZEKOWITZ MD,YUSUF S,et al.Dabigatran versus warfarin in patients with atrial fibrillation[J].N Engl JMed,2009,361(12):1139-1151.
[9]GOMEZ-OUTES A,TERLEIRA-FERNANDEZ AI,CALVO-ROJAS G,et al.Dabigatran,rivaroxaban,or apixaban versus warfarin in patients with nonvalvular atrial fibrillation:a systematic review and meta-analysis of subgroups[J].Thrombosis,2013,2013:640723.
[10]XIONG Q,LAU YC,SENOO K,et al.Non-vitamin K antagonist oral anticoagulants (NOACs) in patients with concomitant atrial fibrillation and heart failure:a systemic review and metaanalysis of randomized trials[J].Eur J Heart Fail,2015,17(11):1192-1200.
[11]LARSEN TB,NIELSEN PB,SKJOTH F,et al.Non-vitamin Kantagonist oral anticoagulants and the treatment of venous thromboembolism in cancer patients:a semi systematic review and meta-analysis of safety and efficacy outcomes[J].PLoS One,2014,9(12):e114445.
[12]KIM IS,KIM HJ,KIM TH,et al.Non-vitamin K antagonist oral anticoagulants have better efficacy and equivalent safety compared to warfarin in elderly patients with atrial fibrillation:a systematic review and meta-analysis[J].J Cardiol,2018,72(2):105-112.
[13]NIELSEN PB,LANE DA,RASMUSSEN LH,et al.Renal function and non-vitamin K oral anticoagulants in comparison with warfarin on safety and efficacy outcomes in atrial fibrillation patients:a systemic review and meta-regression analysis[J].Clin Res Cardiol,2015,104(5):418-429.
[14]SENOO K,LAU YC,DZESHKA M,et al.Efficacy and safety of non-vitamin K antagonist oral anticoagulants vs.warfarin in Japanese patients with atrial fibrillation-meta-analysis[J].Circ J,2015,79(2):339-345.
[15]BEGG CB,MAZUMDAR M.Operating characteristics of a rank correlation test for publication bias[J].Biometrics,1994,50(4):1088-1101.
[16]EGGER M,DAVEY SMITH G,SCHNEIDER M,et al.Bias in meta-analysis detected by a simple,graphical test[J].BMJ,1997,315(7109):629-634.
[17]FLAKER G,EZEKOWITZ M,YUSUF S,et al.Efficacy and safety of dabigatran compared to warfarin in patients with paroxysmal,persistent,and permanent atrial fibrillation:results from the RE-LY(Randomized Evaluation of Long-Term Anticoagulation Therapy)study[J].J Am Coll Cardiol,2012,59(9):854-855.
[18]AL-KHATIB SM,THOMAS L,WALLENTIN L,et al.Outcomes of apixaban vs.warfarin by type and duration of atrial fibrillation:results from the ARISTOTLE trial[J].Eur Heart J,2013,34(31):2464-2471.
[19]STEINBERG BA,HELLKAMP AS,LOKHNYGINA Y,et al Higher risk of death and stroke in patients with persistent vs.paroxysmal atrial fibrillation:results from the ROCKET-AF tria[J].Eur Heart J,2015,36(5):288-296.
[20]LINK MS,GIUGLIANO RP,RUFF CT,et al.Stroke and mortality risk in patients with various patterns of atrial fibrillation:results from the ENGAGE AF-TIMI 48 trial(effective anticoagulation with factor Xa next generation in atrial fibrillation-thrombolysis in myocardial infarction 48)[J].Circ Arrhythm Electrophysiol,2017,10(1):e004267.
[21]PANCHOLY SB,SHARMA PS,PANCHOLY DS,et al.Metaanalysis of gender differences in residual stroke risk and major bleeding in patients with nonvalvular atrial fibrillation treated with oral anticoagulants[J].Am J Cardiol,2014,113(3):485-490.
[22]KAMATH S,CHIN BS,BLANN AD,et al.A study of platelet activation in paroxysmal,persistent and permanent atrial fibrillation[J].Blood Coagul Fibrinolysis,2002,13(7):627-636.
[23]DONG Y,DONG Q.New oral anticoagulants:how do we use them wisely?[J].Curr Cardiol Rep,2015,17(9):626.
[24]VOUKALIS C,LIP GY,SHANTSILA E.Drug-drug interactions of non-vitamin K oral anticoagulants[J].Expert Opin Drug Metab Toxicol,2016,12(12):1445-1461.
[25]张卫芳,鲍慧慧,熊爱珍,等.新型口服抗凝药与抗逆转录病毒药物的相互作用[J].药品评价,2018,15(10):12-15.
[26]冯瑞江,鮑慧慧,熊爱珍,等.新型口服抗凝药与抗癫痫药物的相互作用[J].中国新药与临床杂志,2018,37(8):443-447.
[27]张卫芳,陆社桂,熊淑华,等.达比加群酯联合塞来昔布致上消化道出血1例[J].中国新药与临床杂志,2016,35(8):596-598.
[28]侯微,房德敏,钱皎,等.房颤合并肝硬化患者的口服抗凝药物选择及抗栓策略研究[J].中国现代应用药学,2018,35(10):1549-1553.