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1、,單擊此處編輯母版標(biāo)題樣式,單擊此處編輯母版文本樣式,第二級(jí),第三級(jí),第四級(jí),第五級(jí),2010-6-30,*,替羅非班在,ACS,治療中的應(yīng)用,主 要 內(nèi) 容,替羅非班,概述,替羅非班的臨床研究及指南推薦,STEMI,患者急診介入治療,NSTE-ACS,患者的介入治療,ACS,的早期藥物保守治療,關(guān)于安全性的考慮,2010-7-31,2,PCI,術(shù)后,MACE,風(fēng)險(xiǎn)和治療期間血小板抑制率密切相關(guān),-GOLD,研究,Steinhubl SR,et al.Point-of-care measured platelet inhibition correlates with a reduced ris
2、k of an adverse cardiac event after percutaneous coronary intervention:results of the GOLD(AU-Assessing Ultegra)multicenter study.Circulation,2001 May 29;103(21):2572-8,GOLD,研究給我們提示:,常規(guī)雙聯(lián)抗血小板藥物治療的血小板抑制率,60%,,不能有效降低,MACE,事件,強(qiáng)化抗栓,需要更強(qiáng)有力的抗血小板藥物,GPIIb/IIIa,受體拮抗劑,欣維寧,(鹽酸替羅非班氯化鈉注射液),凝血酶,膠原,5-,羥色胺,腎上腺素,ADP
3、,TXA,2,活化的血小板,COX,抑制劑,ADP,受體,拮抗劑,Gp IIb/IIIa,受體,血小板活化,GPIIb/IIIa,受體拮抗劑,主要抗血小板藥物作用機(jī)制,GPIIb/IIIa,受體拮抗劑,最快速 最直接 最完全 抑制血小板聚集,White HD.,Am J Cardiol.,1997;80(4A):2B-10B.,GPIIb/IIIa,血小板聚集的必經(jīng)之路,ADP,Epinephrine,Collagen,Thrombin,AA,TxA,2,GP IIb/IIIa Expression,Fibrinogen Binding and,Platelet Aggregation,GP
4、IIb/IIIa Expression,GPIIb/IIIa,的作用機(jī)理,抗血栓藥物,抗凝藥,抗血小板藥,環(huán)氧化酶抑制劑,如 阿司匹林,血小板,GPIIb/IIIa,受體拮抗劑,單克隆抗體,abciximab,非肽類(lèi)衍生物,Tirofiban,肽類(lèi),eptifibatide,ADP,抑制劑,氯吡格雷,溶栓藥,Aciximab,Eptifibatide,Tirofiban,結(jié)構(gòu),鼠人,IgG,嵌合體,環(huán)肽,KGD,小分子非肽,RGD,分子量,(,道爾頓,),5000,800,500,GPb/a,選擇性,差,較強(qiáng),較強(qiáng),化學(xué)計(jì)量法,1.5:1,100:1,100:1,血漿半衰期,10-15,分鐘,
5、1.5-2.5,小時(shí),1.5-2.5,小時(shí),受體抑制可逆性,差,(,輸注血小板,),較強(qiáng),(,停藥,),較強(qiáng),(,停藥,),出血發(fā)生率,多,較少,較少,血小板無(wú)力癥,相對(duì)較多,少,少,安全性,相對(duì)較差,相對(duì)較好,相對(duì)較好,價(jià)格,昂貴,相對(duì)較低,相對(duì)較低,適應(yīng)癥,(FDA),PCI,ACS;PCI,ACS;PCI,三種靜脈,GPb/a,受體抑制劑的比較,替羅非班概述,替羅非班的臨床研究及指南推薦,STEMI,患者急診介入治療,NSTE-ACS,患者的介入治療,ACS,的早期藥物保守治療,關(guān)于安全性的考慮,內(nèi) 容,2010-7-31,9,一,.STEMI,急診介入治療,2010-7-31,11,一
6、,.STEMI,急診介入治療,ON TIME-2,在救護(hù)車(chē)或轉(zhuǎn)診中心被確診為急性心梗,(STEMI),ASA+600 mg Clopidogrel+UFH,冠脈造影,替羅非班,安慰劑,導(dǎo)管室,冠脈造影,必要時(shí)使用替羅非班,持續(xù)使用替羅非班,*,N=984,6/2006-11/2007,PCI,*Bolus:25 g/kg&0.15 g/kg/min infusion,Hamm CW et al.Abstract 413-5.Presented April 1,2008,at the American College of Cardiology 57th Annual Meeting in Ch
7、icago,IL.,轉(zhuǎn)運(yùn),On,going,T,irofiban,I,n,M,yocardial Infarction,E,valuation,Results:Primary Endpoint,主要終點(diǎn)事件,Residual ST deviation at 60 min.,60,分鐘的,ST,段殘留移位,mean SD,Placebo,Tirofiban,p-value,可讀,ECG,94.1%,95.5%,0.358,ST,段殘留移位,4.8 6.3,3.3 4.3,0.002,3mm,的,S,T,段殘留移位,44.3%,36.6%,0.026,正常心電圖,30.2%,37.3%,0.031
8、,Hamm CW et al.Abstract 413-5.Presented April 1,2008,at the American College of Cardiology 57th Annual Meeting in Chicago,IL.,2010-7-31,13,累積,ST,段移位與時(shí)間的關(guān)系,Hamm CW et al.Abstract 413-5.Presented April 1,2008,at the American College of Cardiology 57th Annual Meeting in Chicago,IL.,P=0.84,P=0.028,P=0.0
9、22,P=0.02,ON TIME-2,2010-7-31,14,30,天和,1,年的無(wú)事件生存率,Hamm CW et al.Abstract 413-5.Presented April 1,2008,at the American College of Cardiology 57th Annual Meeting in Chicago,IL.,ON TIME-2,P=0.007,100%,95%,90%,85%,80%,0 90 180 270 360,時(shí)間(天),替羅非班,安慰劑,P=0.012,90%,80%,70%,60%,50%,40%,0 5 10 15 20 25 30,時(shí)間(
10、天),替羅非班,安慰劑,00000,00000,00000,2010-7-31,15,MACE,與出血事件發(fā)生率,Hamm CW et al.Abstract 413-5.Presented April 1,2008,at the American College of Cardiology 57th Annual Meeting in Chicago,IL.,ON TIME-2,聯(lián)合終點(diǎn):,Death/MI/TVR/Stroke/Thromb bailout,2010-7-31,16,ON TIME-2,的,提示,提前,應(yīng)用,高負(fù)荷劑量,的替羅非班對(duì),ST,EMI,是安全有效的,可顯著提高近
11、期和遠(yuǎn)期生存率,不增加出血風(fēng)險(xiǎn),急性,ST,段抬高型心肌梗死指南推薦,血小板,GPIIb/III a,拮抗劑中替羅非班在中國(guó)使用最為普遍。,2010-7-31,18,急性,ST,段抬高型心肌梗死,計(jì)劃采取直接,PCI,的患者,無(wú)論是否提前使用氯吡格雷,都可以聯(lián)合使用一種,GPIIb/IIIa,受體拮抗劑(沒(méi)有提前使用氯吡格雷的,IIa A,;提前使用氯吡格雷,IIa B,),對(duì)于計(jì)劃行直接,PCI,,且無(wú)使用禁忌的患者,可常規(guī)使用一種,GPIIb/IIIa,受體拮抗劑,(,IIb B,),2012 ESC STEMI GUIDELINE,2011 ACC PCI GUIDELINE,,,P34
12、,2010-7-31,19,2012 ESC STEMI GUIDELINE,對(duì)于高缺血風(fēng)險(xiǎn)擬進(jìn)行轉(zhuǎn)運(yùn),PCI,的患者可考慮上游使用,GPIIb/IIIa,受體拮抗劑(區(qū)別于導(dǎo)管室內(nèi)應(yīng)用)(,IIb B,),GPIIb/IIIa,受體拮抗劑的使用應(yīng)充分評(píng)估患者缺血和出血風(fēng)險(xiǎn)的凈獲益。聯(lián)合肝素時(shí),應(yīng)調(diào)整肝素的使用劑量(,5060U/kg,),2012 ESC STEMI GUIDELINE,P17,急性,ST,段抬高型心肌梗死,二、,NSTE-ACS,患者的介入治療,2010-7-31,21,二、,NSTE-ACS,患者的介入治療,0.005 0.1 1 10 200,替羅非班較好 對(duì)照組較好,
13、Marco Valgimigli,et al.,Tirofiban as adjunctive therapy for acute coronary syndromes and percutaneous coronary intervention:a meta-analysis of randomized trials.European Heart Journal(2010)31,3549,.,薈萃研究證實(shí):,使用替羅非班可以降低,NSTE-ACS,行,PCI,治療患者,30,天死亡,/,心梗事件發(fā)生率,,,上游用藥效果尤其顯著,2010-7-31,22,ASA Heparin,Thyenop
14、iridine,Tirofiban,0.4,g/kg/min X 30 min,followed by 0.10,g/kg/min up to 12 hours,1,2,3,Intent to PTCA/stent,between 24 and 48 hours,Intent to PTCA/stent,between 24 and 48 hours,+HBD Tirofiban,Intent to PTCA/stent,between 24 and 48 hours,+Abciximab,ASA Heparin,Thyenopiridine,ASA Heparin,Thyenopiridin
15、e,High-risk,NSTEMI,ACS,Bolognese L et al.:JACC 2005,in press,EVEREST,試驗(yàn)設(shè)計(jì),2010-7-31,23,P,=0.0009,P,=0.015,PCI前后TMPG,P,=NS,P,=0.015,P,=0.0002,PCI,前后,cTn-I,峰值,EVEREST,研究結(jié)果,Bolognese L et al.:JACC 2005,in press,2010-7-31,24,臨床提示,上游,使用標(biāo)準(zhǔn)劑量替羅非班對(duì)高危,NSTEMI,患者可以改善其心肌灌注水平,減少有害心肌損害標(biāo)記物釋放??山档托募p害程度,給高?;颊邘?lái)更大獲益。
16、,高劑量替羅非班可以獲得和阿昔單抗相類(lèi)似的臨床效果。,Randomized Comparison Upstr,E,am Standard Dose Tirofiban,V,ersus Downstr,E,am High-do,S,e,T,irofiban or Abciximab in High-risk ACS Treated With PCI,Bolognese L et al.:JACC 2005,in press,不穩(wěn)定心絞痛,/,非,ST,段抬高心肌梗死指南推薦,在血小板,GPIIb/IIIa,受體拮抗劑中以替羅非班在中國(guó)的使用最為普遍。與阿昔單抗不同,替羅非班的可逆性好、停藥后血小板功能恢復(fù)快;抗原性弱,血小板減少癥發(fā)生率較低。,Class I,(,I,類(lèi)推薦),(,2011,年),對(duì)于確診為中,/,高危且選擇早期有創(chuàng)策略的,UA/NSTEMI,患者,應(yīng)在入院后接受雙聯(lián)抗血小板治療(,A,)。阿司匹林應(yīng)在入院后就開(kāi)始使用(,A,)。入院后在阿司匹林的基礎(chǔ)上加用的另外一種抗血小板治療可從如下方案中選擇:,更新對(duì)治療的定義更加明確:對(duì)于中,/,高危的,UA/NSTEMI,患者,