单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,血小板糖蛋白IIb/IIIa受体拮抗剂在介入/非介入患者中的应用,浙江大学医学院附属第二医院 心脏中心,王建安,血小板糖蛋白IIb/IIIa受体拮抗剂在介入/非介入患者中的,1,基本原理,分子结构,适应症和循证医学,结论,基本原理,2,血小板GPIIb/IIIa受体拮抗剂的作用机理,Mechanism,Competitive antagonist of the GP receptor on the platelet surface for adhesive proteins such as fibrinogen,VWF,maximally inhibit the final common pathway involved in platelet aggregation,Collagen,ADP,Thromboxane A2,Platelet Activation,platelet aggregation,Thrombus formation,GPIIb/IIIa inhibitor,Aspirin,COX,Ticlopidin,Clopidogrel,血小板GPIIb/IIIa受体拮抗剂的作用机理 Mechan,3,血小板糖蛋白IIbIIIa受体拮抗剂在介入非介入患者中的应用-课件,4,目前的GPIIb/IIIa受体拮抗剂依据化学结构的不同可分为三类,1.单克隆抗体,，Abciximab（阿昔单抗），最早应用于临床的GPIIb/IIIa受体拮抗剂，是GPIIb/IIIa受体的单克隆抗体，通过占据受体的位置而阻断血小板聚集反应。,2.肽类抑制剂,，Eptifibatide（埃替非巴肽），是一类含有GPIIb/IIIa受体识别序列的低分子多肽。,3.非肽类抑制剂,，静脉的Tirofiban（替罗非班），是肽衍生物，其药理性质与埃替非巴肽相似。口服非肽类抑制剂，Xemilofiban、Orbofiban、Rocifiban、Sibrafiban、Lefradafiban、但试验结果均以失败告终。,目前的GPIIb/IIIa受体拮抗剂依据化学结构的不同可分为,5,三类,GPIIb/IIIa受体拮抗剂的化学结构,三类 GPIIb/IIIa受体拮抗剂的化学结构,6,STEMI,Clinical finding,EKG,Serum markers,Risk assessment,Non-cardiacchest pain,Stableangina,UA,NSTEMI,Negative,Positive,ST-T wave changes,ST elevation,Lowprobability,Medium-high,risk,ThrombolysisPrimary PCI,Aspirin+GP IIb/IIIa inhibitor,clopidogrel+heparin/,LMWH+anti-ischemic RxEarly invasive Rx,Discharge,Negative,Diagnostic rule out MI/ACS,pathway,STEMI,Negative,Atypical,pain,Low,risk,Aspirin,heparin/low-molecular-weight heparin(LMWH)+clopidogrelAnti-ischemic Rx Early conservative therapy,Ongoing pain,DM=diabetes mellitus.,Cannon,Braunwald.,Heart Disease,.2019.,Rest pain,Post-MI,DM,Prior Aspirin,Exertional pain,The Spectrum of ACS,STEMIClinical findingEKGSerum,7,Benefit of GP IIb/IIIa Blockade in ACS,Meta-Analysis of Six Major Trials(31,402 Patients),All patients with ACS,Patients with ACS,undergoing PCI,within 5 days,Boersma E et al.Lancet 2019,0.5,0.6,0.7,1.1,Anti GPIIb/IIIa better,0.8,0.9,1.0,Relative 30-Day Risk of,Death and MI,Benefit of GP IIb/IIIa Blockad,8,PRISM(3232)7.1%5.8%,0.800.60-1.06,PRISM-PLUS(1915)12.0%8.7%0.700.50-0.98,PARAGON-A(2282)11.7%(l)10.3%0.870.58-1.29(h)12.3%1.060.72-1.55,PURSUIT(10,948)15.7%14.2%0.890.79-1.00,PARAGON-B(5225)11.4%10.6%0.920.77-1.09,GUSTO-IV(7800)8.0%(24h)8.2%1.020.83-1.24 (48h)9.1%1.150.94-1.39,Odds Ratio,Placebo,IV GP IIb/IIIa,95%CI,*With/without heparin.,Without heparin.,(l)=low dose.,(h)=high-dose.,Adapted from:Boersma E,et al.,Lancet.,2019;359:189-198.,Placebo Better,GP IIb/IIIa Better,Odds Ratio(95%CI),0.0,1.0,2.0,Study(n),GP IIb/IIIa Inhibitors in UA/NSTEMI:Death or MI at 30 Days,PRISM(3232)7.1%5.8%0.8,9,Favors Control,Favors Treatment,Year,CAPTURE,2019,RESTORE,2019,EPISTENT,2019,2019,CADILLAC-P,2019,ADMIRAL,2019,RAPPORT,2019,Petronio,2019,CADILLAC-S,2019,0.01,0.1,1,10,100,Study,ERASER,2019,ISAR-2,2000,EPIC,Risk Ratio and 95%CI,RR 0.79,Z=-2.27,2P=0.023,EPILOG,2019,ESPRIT,2019,Overall,Tamburino,2019,N,1265,2141,1603,2099,1046,300,483,89,1036,225,401,2792,2064,15,651,107,Karvouni E,et al.,J Am Coll Cardiol.,2019;41:26-32.,Intravenous GP IIb/IIIa Receptor Antagonists Reduce Mortality after PCI,Favors ControlFavors Treatment,10,Kong D,et al.,Am J Cardiol,.2019;92:651-655.,Placebo Better,IIb/IIIa Better,Trial,Control,Treatment,N,0.1,1,10,RESTORE,1.1%,0.9%,12,940,EPILOG,1.2%,0.9%,4891,RAPPORT,1.3%,1.0%,5374,CAPTURE,1.3%,1.0%,6639,EPIC,1.7%,1.5%,2099,1.3%,IMPACT I,1.0%,6789,1.2%,IMPACT II,0.9%,10,799,ESPRIT,1.0%,0.8%,17,403,ISAR-2,1.1%,0.8%,17,804,ADMIRAL,1.2%,0.8%,18,104,EPISTENT,1.1%,0.8%,15,339,1.3%,CADILLAC,0.9%,20,186,Odds Ratio and 95%CI,0.73(0.55,0.96),P,=0.024,Meta-analysis of Survival with Platelet GP IIb/IIIa Antagonists for PCI,Kong D,et al.Am J Cardiol.2,11,ACCP-7对NSTE ACS 治疗建议：NSTE ACS的中、高危患者早期治疗，在应用阿司匹林及肝素基础上，加用Eptifibatide 或Tirofiban（1A级）；同时应用氯吡格雷的中、高危患者，早期加用Eptifibatide 或Tirofiban（2A级）。,急性冠状动脉综合征（ACS）中的应用,ACCP-7对NSTE ACS 治疗建议：NSTE ACS的,12,ACC/AHA 2019年UA/NSTEMI指南,预行,PCI,的UA/NSTEMI患者，术前可应用,GPb/受体拮抗剂,（I/A）,对可能行,PCI,的患者，,阿昔单抗,是上游GPb/a受体拮抗剂的首选药物，否则,依替巴肽或替罗非班,是首选的药物,（I/B）,UA/NSTEMI的,高危患者,行,PCI,，应给予静脉内,GPIIb/IIIa拮抗剂,（I/A）,对于选择,保守策略,的UA/NSTEMI患者，可应用,依替巴肽或替罗非班,进行抗凝治疗,（b/B）,阿昔单抗,不应当应用于不准备行PCI的患者,（/A）,ACC/AHA 2019年UA/NSTEMI指南预行PCI的,13,ESC 2019 年UA/NSTEMI指南,GPb/a受体拮抗剂,应该和抗凝药物,联合应用,（I/A）,在未预先使用GPb/a受体拮抗剂而计划进行,PCI,的高危患者，建议在CAG后,立即使用阿昔单抗,（I/A），,这种情况下依替巴肽或替罗非班的使用价值较低,（a/B）,中高危,的UA/NSTEMI患者，建议在使用口服抗血小板药物的基础上，,加用依替巴坦或替罗非班,治疗,（a/A）,在CAG前的初始治疗中使用依替巴肽或替罗非班者，PCI术中和术后应,维持应用原来的药物,（a/B）,ESC 2019 年UA/NSTEMI指南GPb/a,14,2019年ACC/AHA/SCAI 关于UA/NSTEMI的PCI指南,UA/NSTEMI患者接受,PCI术,时，应用静脉GPb/a拮抗剂是,有效,的,(I/C),如果PCI术时给予,氯吡格雷,治疗，同时,联合应用GPb/a 受体拮抗,剂的抗血小板,效果更好,（IIa/B）,对阿司匹林有绝对禁忌症的患者，应在PCI术前至少6小时给予300600mg负荷剂量的氯吡格雷；和/或PCI时给予GPb/a 受体拮抗剂,(IIa/C),2019年ACC/AHA/SCAI 关于UA/NSTEMI的,15,GPb/a受体拮抗剂在STEMI溶栓中的应用,全剂量,溶栓剂与GP b/a受体拮抗剂合用再灌注率提高，但,出血风险明显增加,SPEED和GUSTO-Pilot试验显示，Abciximab与,半量t-PA,合用，显著提高梗死相关血管开通率，,但出血风险仍高于溶栓组,GPb/a受体拮抗剂在STEMI溶栓中的应用全剂量溶栓剂,16,0,0.5,1,1.5,Relative,Risk of Death+MI+TVR,Abciximab vs Control,30 Days,6 Months,RAPPORT,Brener et al.,(PTCA),Circulation 2019,ISAR-2,Neumann et al.,(Stent),J Am Coll Cardiol 2000,ADMIRAL,M