冠心病合并房颤患者的抗栓治疗.ppt

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,冠心病合并房颤患者的抗栓治疗,一、房颤的危害,Percent of subject,died in follow-up,years,Benjamin EJ,Circulation 1998;946,10%,30%,50%,0,1,3,4,6,5,2,7,8,9,10,70%,Women,No AF,Men,AF,Women,AF,Men,No AF,men,women,Odds,Ratio,for Death,1.2-1.8,1.5-2.2,房颤的危害死亡率增加,男性死亡率增加,1.9,倍,女性死亡率增加,1.5,倍,房颤的危害,脑卒中危险持续存在,Framingham,心脏研究,房颤患者一生中卒中几率为35%,房颤的发生率,随年龄增长而增加,Go AS,et al.JAMA.2001;285:2370-2375,60岁后每10年增加1倍,脑卒中,25-30%,是由房颤引起,欧美国家,60-80%,的房颤患者接受抗凝,非风心病房颤，血栓危险增加,6,倍，约占脑血管意外的,1520%,风心病房颤：血栓危险增加,18倍,栓塞的总发生率,5%,/,年,国内三甲大医院、房颤患者,7%,接受抗凝,全国整体医院调查，房颤患者,2%,接受抗凝,房颤血栓栓塞风险与抗凝现状,二、房颤抗栓药物治疗,阿司匹林与华法林作用机制比较,阿司匹林抑制血小板聚集，虽然对心房血栓的预防作用差于抗凝药物，故主要针对动脉粥样硬化性脑血栓形成（,platelet-rich thrombi,），,预防,TIA,及轻度的缺血性脑卒中的发生。,华法林主要预防心源性血栓栓子引起的严重的脑栓塞：房颤形成的血栓主要是由于凝血因素异常（心房内皮功能受影响、血流迟缓等），在左心房或下肢静脉形成所致（,fibrin-rich thrombi,）,Prior stroke or TIA 2,(should be 3),10,Age 75 years 1 28,Hypertension 1 65,Diabetes mellitus 1 18,Heart failure 1 32,High risk4,6 9,Moderate risk2,3 40,Low risk0,1 51,Van Walraven C et al.,Arch Intern Med,2003;,163,:93643,*Nieuwlaat R et al.,Eur Heart J,2006(E-published),发生率,(%)*,房颤卒中危险积分,:,-,CHADS2,指数,危险积分,(,分,),抗栓治疗最危险并发症,-,颅内出血,抗凝治疗中脑卒中发生率大约,1%,Aspirin,使,ICH,危险增加近,40%,（即从,0.15-0.3%,增加至,0.2-0.4%,）,Warfarin(INR 23),使,ICH,危险增加一倍，达,0.30.6%/,年,抗凝治疗中,ICH,的发生造成严重危害,Hart RG et al.,Stroke,2005;,36,:158893,SPAFIII,试验：,1044,例患者随机分组华法林标准抗凝组和阿司匹林低抗凝、固定剂量华法林（联合治疗组）,联合治疗组与华法林标准抗凝组比较,缺血性脑卒中和体循环栓塞发生率,7.9,vs,1.9,（,p160/100,既往服用,VKA,发生严重出血史，酗酒,2 years,消化道溃疡,血小板减少症,长期需要服用,NSAID,ACTIVE A,ACTIVE W,N,7554,6706,平均年龄,(years),71 10,70 9,男性,58%,66%,平均收缩,BP(mmHg),136 19,133 19,持续,AF,64%,68%,Baseline VKA use,8.5%,77%,Baseline aspirin use,83%,26%,既往,MI,史,14%,18%,既往 卒中 或,TIA,史,13%,15%,平均,CHADS2,积分,2.0 1.1,2.0 1.1,基线情况,(ACTIVE-A),(ACTIVE-A),(ACTIVE-A),Conclusions,对不适合服用,VKA,的高危,AF,病人，,aspirin,加服,clopidogrel,可以,:,减少主要血管事件,主要是卒中的减少,伴随大出血的增加,对大多病人提供重要益处，增加可接受的危险,(ACTIVE-A),长期口服抗凝药的房颤患者,冠脉支架术后抗血栓治疗,患者接受,PCI,时应,暂停用,VKA,，以减少穿刺局部出血并发症，,术后应尽快恢复,，并将,INR,调节至治疗值。,早期,应用阿司匹林、波立维、华法林,三联,抗栓治疗。之后维持应用波立维,75mg/,天和华法林（,INR 2-3,）。,波立维应用：,BMS,至少,1,个月，雷帕霉素洗脱支架至少,3,个月，紫杉醇洗脱支架至少,6,个月，特殊病人应用,12,个月。,之后如果没有冠脉事件，单独应用华法林维持。与阿司匹林,/,波立维合用时，严密监测,INR,II b/C,长期口服抗凝药的患者,(,主要房颤患者,),冠脉支架术后抗血栓治疗专家共识,1.,首先评价患者的出血风险,门诊出血危险指数,（,最高,4,分,）：,如存在以下危险因素,每项计,1,分,：年龄,65,岁、既往脑卒中病史、既往出血史；,如存在以下危险因素其中,任何一项计,1,分,：红细胞比容,1.5mg/dL,或糖尿病,评分为,0,时,年出血风险为,3%,，为低危患者；,评分为,1-2,时,年出血风险为,8-12%,，为中危患者；,评分为,3-4,时,年出血风险为,30-48%,，为高危患者。,2.,之后结合冠心病临床情况和支架类型选择抗栓方案,:,出血风险,临床情况,支架,专 家 推 荐,低、中危,择期,BMS,术后,1,个月,：,华法林,（,INR 23,）,+,阿司匹林,（,100mg/,天）,+,氯吡格雷,（,75mg/,天）,+PPI,之后,：,W,（,INR 23,）。,择期,DES,术后,3,个月,:,（雷帕霉素支架）或,6,个月（紫杉醇支架）,:,三联,+PPI,术后,36,月后,-12,个月：,W,（,INR 23,）,+C,之后：,W,（,INR 23,）,ACS,BMS,或,DES,术后,6,个月：,三联,+PPI,术后,612,个月：,W,（,INR 23,）,+C,之后：,W,（,INR 23,）,高危,（建议仅应用,BMS,）,择期,BMS,术后,24,周：,三联,+PPI,24,周后：,华法令,（,INR 23,）。,ACS,BMS,术后,24,周：,三联,+PPI,术后,24,周到,12,个月：,W,（,INR 23,）,+C,之后：,W,（,INR 23,）,五、新的抗凝药物研究,口服抗凝新药开发,西美加群（,Ximelagatran,）（,II,因子抑制剂）,达美加群（,Dabigatran,）（,II,因子抑制剂）,阿哌沙班（,Rivaroxaban,）,（,X,因子抑制剂）,艾吡沙班（,Apixaban,）,（,X,因子抑制剂）,研发中的,IIa,因子抑制剂,Ximelagatran,Dabigatran,口服制剂,静脉制剂,Adapted from Weitz&Bates,J Thromb Haemost,2005,Hirudin,Bivalirudin,Argatraban,Xa,IIa,TF/VIIa,X,IX,IXa,VIIIa,Va,II,Fibrin,Fibrinogen,SPORTIF III,：,多中心、随机、临床试验（,3410,例）,SPORTIF V,：,多中心、随机双盲临床试验（,3922,例）,入选病人：至少有一个脑卒中危险因素的房颤患者,主要终点：脑卒中（缺血性、出血性）和体循环栓塞,华法林组：（,INR 2.0-3.0,）,西美加群,Ximelagatran,组：（,36mg bid,）,主要终点事件发生率：,Ximelagatran,低于华法林（,p 0.05,）,总出血事件发生率：,Ximelagatran,显著低于华法林（,p 0.01,）,暂时性肝转氨酶升高：,Ximelagatran,明显高于华法林,SPORTIF,临床试验,The RE-LY Study:Randomized Evaluation of Long-term anticoagulant therapY,达比加群与华法林在,18,113,例房颤合并脑卒中风险患者的对比研究,RE-LY Study,RE-LY:A Non-inferiority Trial,房颤伴,1,危险因素,无抗凝禁忌证,44,个国家,951,个 中心,R,华法林,(INR 2.0-3.0),N=6000,达比加群前体,Etexilate,110 mg b.i.d.,N=6000,达比加群前体,Etexilate,150 mg b.i.d.,N=6000,前瞻、随机,1,0,有效性终点,=,卒中或全身栓塞,1,0,安全性终点,=,大出血,开放,盲法,Baseline Characteristics,Characteristic,Dabigatran 110 mg,Dabigatran 150 mg,Warfarin,Randomized,6015,6076,6022,Mean age(years),71.4,71.5,71.6,Male(%),64.3,63.2,63.3,CHADS2 score(mean),0-1 (%),2 (%),3+(%),2.1,32.6,34.7,32.7,2.2,32.2,35.2,32.6,2.1,30.9,37.0,32.1,Prior stroke/TIA(%),19.9,20.3,19.8,Prior MI(%),16.8,16.9,16.1,CHF(%),32.2,31.8,31.9,Baseline ASA(%),40.0,38.7,40.6,Warfarin Nave(%),49.9,49.8,51.4,卒中或全身栓塞,0.50,0.75,1.00,1.25,1.50,达比加群,110 vs.,华法林,达比加群,150 vs.,华法林,Non-inferiority,p-value,0.001,0.001,Superiority,p-value,0.34,0.001,Margin=1.46,HR (95%CI),卒中或全身栓塞,Cumulative Hazard Rates,0.0,0.01,0.02,0.03,0.04,0.05,0,0.5,1.0,1.5,2.0,2.5,Dabigatran110,Dabigatran 150,Warfarin,6022,5862,5718,4593,2890,1322,6015,5862,5710,4593,2945,1385,6076,5939,5779,4682,3044,1429,No.at Risk,W,D110,D150,Years,所有颅内出血,Years,Cumulative Hazard Rates,0.0,0.01,0.02,0.03,0.04,0,0.5,1.0,1.5,2.0,2.5,Dabigatran110,Dabigatran150,Warfarin,#at Risk,Year 0.5,1.0,1.5,2.0,2.5,D110,D150,W,6015,5900,5771,4666,3006,1420,6076,5958,5817,4735,3080,1451,6022,5887,5759,4632,2933,1343,出血和临床净获益,D,110mg,D,150mg,warfarin,D 110mg vs.Warfarin,D 150mg vs.Warfarin,Annual,rate,Annual,rate,Annual,rate,RR,95%CI,P,RR,95%CI,p,大出血,2.7%,3.1%,3.4%,0.80,0.69-0.93,0.003,0.93,0.81-1.07,0.31,危机生命的大出血,1.2%,1.5%,1.8%,0.68,0.55-0.83,0.001,0.81,0.66-0.99,0.04,小出血,13.2%,14.8%,16.4%,0.79,0.74-0.84,0.001,0.91,0.85-0.97,0.005,全部出血,(Major+Minor),14.6,16.4,18.2,0.78,0.74-0.83,90%power to show non-inferiority,(apixaban vs warfarin upper bound of 95%CI 1.38),随机、双盲,(n=15,000),Age 75 years,Prior stroke,TIA or SE,CHF or LVEF 40%,Diabetes mellitus,Hypertension,Warfarin/warfarin placebo adjusted by INR/sham INR,based on encrypted point-of-care testing device,谢谢！,研发中的抗凝药物,TFPI(tifacogin),Fondaparinux,Idraparinux,RivaroxabanApixaban,LY517717YM150,DU-176bPRT-054021,Ximelagatran,Dabigatran,口服制剂,静脉制剂,DX-9065aOtamixaban,AT,APC,sTM(ART-123),Adapted from Weitz&Bates,J Thromb Haemost,2005,TTP889,Hirudin,Bivalirudin,Argatraban,Xa,IIa,TF/VIIa,X,IX,IXa,VIIIa,Va,II,Fibrin,Fibrinogen,