血小板糖蛋白iibiiia受体拮抗剂在介入非介入患者中的应用ppt课件

1、血小板糖蛋白IIb/IIIa受体拮抗剂在介入/非介入患者中的运用.根本原理分子构造顺应症和循证医学结论.血小板GPIIb/IIIa受体拮抗剂的作用机理 MechanismCompetitive antagonist of the GP receptor on the platelet surface for adhesive proteins such as fibrinogen, VWFmaximally inhibit the final common pathway involved in platelet aggregation Collagen ADP Thromboxane A2P

2、latelet Activationplatelet aggregationThrombus formationGPIIb/IIIa inhibitorAspirinCOXTiclopidinClopidogrel.目前的GPIIb/IIIa受体拮抗剂根据化学构造的不同可分为三类 1.单克隆抗体，Abciximab阿昔单抗，最早运用于临床的GPIIb/IIIa受体拮抗剂，是GPIIb/IIIa受体的单克隆抗体，经过占据受体的位置而阻断血小板聚集反响。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Tirofib

3、an替罗非班，是肽衍生物，其药理性质与埃替非巴肽类似。口服非肽类抑制剂，Xemilofiban、Orbofiban、Rocifiban、Sibrafiban、Lefradafiban、但实验结果均以失败告终。.三类 GPIIb/IIIa受体拮抗剂的化学构造.STEMIClinical findingEKGSerum markersRisk assessmentNon-cardiacchest painStableanginaUANSTEMINegativePositiveST-T wave changesST elevationLowprobabilityMedium-high riskThr

4、ombolysisPrimary PCIAspirin + GP IIb/IIIa inhibitor clopidogrel + heparin/LMWH + anti-ischemic RxEarly invasive RxDischargeNegativeDiagnostic rule out MI/ACS pathwaySTEMI NegativeAtypical painLow riskAspirin, heparin/low-molecular-weight heparin (LMWH) + clopidogrelAnti-ischemic Rx Early conservativ

5、e therapyOngoing painDM=diabetes mellitus.Cannon, Braunwald. Heart Disease. 2001.Rest pain, Post-MI, DM, Prior AspirinExertional painThe Spectrum of ACS.Benefit of GP IIb/IIIa Blockade in ACSMeta-Analysis of Six Major Trials (31,402 Patients)All patients with ACSPatients with ACS, undergoing PCI wit

6、hin 5 daysBoersma E et al. Lancet 2001.1Anti GPIIb/IIIa betterRelative 30-Day Risk of Death and MI.PRISM (3232)7.1%5.8% 0.800.60-1.06PRISM-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% 1.060.72-1.55PURSUIT (10,948)15.7%14.2% 0.890.79-1.00

7、PARAGON-B (5225)11.4%10.6% 0.920.77-1.09GUSTO-IV (7800)8.0%(24h)8.2% 1.020.83-1.24 (48h)9.1% 1.150.94-1.39Odds RatioPlaceboIV GP IIb/IIIa95% CI*With/without heparin.Without heparin.(l)=low dose.(h)=high-dose.Adapted from: Boersma E, et al. Lancet. 2002;359:189-198.Placebo BetterGP IIb/IIIa BetterOdd

8、s Ratio (95% CI)0.01.02.0Study (n)GP IIb/IIIa Inhibitors in UA/NSTEMI: Death or MI at 30 Days.Favors ControlFavors TreatmentYearCAPTURE1997RESTORE1998EPISTENT19991997CADILLAC-P2002ADMIRAL2001RAPPORT1998Petronio2002CADILLAC-S20020.010.1110100StudyERASER1999ISAR-22000EPICRisk Ratio and 95% CIRR 0.79Z=

9、-2.272P=0.023EPILOG1999ESPRIT2002OverallTamburino2002N126521411603209910463004838910362254012792206415,651107Karvouni E, et al. J Am Coll Cardiol. 2003;41:26-32.Intravenous GP IIb/IIIa Receptor Antagonists Reduce Mortality after PCI.Kong D, et al. Am J Cardiol. 2003; 92:651-655.Placebo BetterIIb/III

10、a BetterTrialControlTreatmentN0.1110RESTORE1.1%0.9%12,940EPILOG1.2%0.9%4891RAPPORT1.3%1.0%5374CAPTURE1.3%1.0%6639EPIC1.7%1.5%20991.3%IMPACT I1.0%67891.2%IMPACT II0.9%10,799ESPRIT1.0%0.8%17,403ISAR-21.1%0.8%17,804ADMIRAL1.2%0.8%18,104EPISTENT1.1%0.8%15,3391.3%CADILLAC 0.9%20,186Odds Ratio and 95% CI0

11、.73 (0.55, 0.96)P=0.024Meta-analysis of Survival with Platelet GP IIb/IIIa Antagonists for PCI.ACCP-7对NSTE ACS 治疗建议：NSTE ACS的中、高危患者早期治疗，在运用阿司匹林及肝素根底上，加用Eptifibatide 或Tirofiban1A级；同时运用氯吡格雷的中、高危患者，早期加用Eptifibatide 或Tirofiban2A级。 急性冠状动脉综合征ACS中的运用.ACC/AHA 2007年UA/NSTEMI指南预行PCI的UA/NSTEMI患者，术前可运用GPb/受体拮抗剂

12、I/A 对能够行PCI的患者，阿昔单抗是上游GPb/a受体拮抗剂的首选药物，否那么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 对于选择保守战略的UA/NSTEMI患者，可运用依替巴肽或替罗非班进展抗凝治疗b/B阿昔单抗不该当运用于不预备行PCI的患者/A.ESC 2007 年UA/NSTEMI指南GPb/a受体拮抗剂应该和抗凝药物结合运用I/A在未预先运用GPb/a受体拮抗剂而方案进展PCI的高危患者，建议在CAG后立刻便用阿昔单抗I/A，这种情况下依替巴肽或替罗非班的运用价值较低a/B中高危的UA/NSTEMI患

13、者，建议在运用口服抗血小板药物的根底上，加用依替巴坦或替罗非班治疗a/A 在CAG前的初始治疗中运用依替巴肽或替罗非班者，PCI术中和术后应维持运用原来的药物a/B.2007年ACC/AHA/SCAI 关于UA/NSTEMI的PCI指南 UA/NSTEMI患者接受PCI术时，运用静脉GPb/a拮抗剂是有效的 (I/C)假设PCI术时给予氯吡格雷治疗，同时结合运用GPb/a 受体拮抗剂的抗血小板效果更好IIa/B对阿司匹林有绝对忌讳症的患者，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).GPb/a受体拮抗剂在STEMI溶栓

14、中的运用全剂量溶栓剂与GP b/a受体拮抗剂合用再灌注率提高，但出血风险明显添加SPEED和GUSTO- Pilot实验显示，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.00.511.5Relative Risk of Death+MI+TVRAbciximab vs Control30 Days6 Months RAPPORT, Brener et al.(PTCA)Circulation 1999ISAR-2Neumann et al. (Stent)J Am Coll Cardiol 2000ADMIRALMontalescot et al(

15、Stent) N Engl J Med, 2001CADILLACStone et al.(Stent/PTCA) N Engl J Med, 2002ACEAntoniucci et al.(Stent) J Am Coll Cardiol 2003PooledAbciximab for PCI in AMI00.511.5GP IIb/IIIa受体拮抗剂在AMI患者PCI中的运用.ACC/AHA 2007年关于STEMI的PCI指南对于已接受抗凝、拟行PCI的患者, 术前运用UFH者，根据手术需求可予以UFH再次静脉bolus,但同时应思索GPb/a受体拮抗剂的协同抗凝效应 (I/C).G

16、PIIb/IIIa受体拮抗剂在PCI中的早期运用 ELISA I 、EVEREST 、TIGER-PA、ONTIME 研讨证明在PCI患者中，早期运用急诊室、监护室或院前GPIIb/IIIa受体拮抗剂tirofiban效果优于晚期运用导管室.ACC 2021：ON-TIME-2：Ongoing-Tirofiban In Myocardial Infarction EvaluationAcute myocardial infarctiondiagnosed in ambulance or referral centerASA+600 mg ClopidogrelAngiogramTirofiba

17、n *PlaceboTransportationPCI centreAngiogramTirofibanprovisionalTirofiban contdN=9846/2006-11/2007PCI*Bolus: 25 g/kg & 0.15 g/kg/min infusion.Results: Primary EndpointResidual ST deviation at 60 minmean SDPlaceboTirofibanp- valueReadable ECG94.1%95.5%0.358ResidualST - deviation (mm)4.8 6.33.3 4.30.00

18、2 3 mm ST-deviation44.3%36.6%0.026normal ECG30.2%37.3%0.031.Residual ST 3 mm (combined)Placebo betterTirofiban betterAll patients (PCI)Male genderFemale genderDiabetesNo diabetesTIMI risk 3TIMI risk 3Age median value0.1110Primary EndpointSubgroups.Event-free SurvivalOngoing Tirofiban In Myocardial Infaction EvaluationP = 0.0