血小板糖蛋白iibiiia受體拮抗劑在介入非介入患者中的應(yīng)用ppt課件

1、血小板糖蛋白IIb/IIIa受體拮抗劑在介入/非介入患者中的運(yùn)用.根本原理分子構(gòu)造順應(yīng)癥和循證醫(yī)學(xué)結(jié)論.血小板GPIIb/IIIa受體拮抗劑的作用機(jī)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受體拮抗劑根據(jù)化學(xué)構(gòu)造的不同可分為三類 1.單克隆抗體，Abciximab阿昔單抗，最早運(yùn)用于臨床的GPIIb/IIIa受體拮抗劑，是GPIIb/IIIa受體的單克隆抗體，經(jīng)過(guò)占據(jù)受體的位置而阻斷血小板聚集反響。2.肽類抑制劑，Eptifibatide埃替非巴肽，是一類含有GPIIb/IIIa受體識(shí)別序列的低分子多肽。3.非肽類抑制劑，靜脈的Tirofib

3、an替羅非班，是肽衍生物，其藥理性質(zhì)與埃替非巴肽類似?？诜请念愐种苿?，Xemilofiban、Orbofiban、Rocifiban、Sibrafiban、Lefradafiban、但實(shí)驗(yàn)結(jié)果均以失敗告終。.三類 GPIIb/IIIa受體拮抗劑的化學(xué)構(gòu)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對(duì)NSTE ACS 治療建議：NSTE ACS的中、高危患者早期治療，在運(yùn)用阿司匹林及肝素根底上，加用Eptifibatide 或Tirofiban1A級(jí)；同時(shí)運(yùn)用氯吡格雷的中、高?；颊?，早期加用Eptifibatide 或Tirofiban2A級(jí)。 急性冠狀動(dòng)脈綜合征ACS中的運(yùn)用.ACC/AHA 2007年UA/NSTEMI指南預(yù)行PCI的UA/NSTEMI患者，術(shù)前可運(yùn)用GPb/受體拮抗劑

12、I/A 對(duì)能夠行PCI的患者，阿昔單抗是上游GPb/a受體拮抗劑的首選藥物，否那么依替巴肽或替羅非班是首選的藥物I/B UA/NSTEMI的高?；颊咝蠵CI，應(yīng)給予靜脈內(nèi)GPIIb/IIIa拮抗劑 I/A 對(duì)于選擇保守戰(zhàn)略的UA/NSTEMI患者，可運(yùn)用依替巴肽或替羅非班進(jìn)展抗凝治療b/B阿昔單抗不該當(dāng)運(yùn)用于不預(yù)備行PCI的患者/A.ESC 2007 年UA/NSTEMI指南GPb/a受體拮抗劑應(yīng)該和抗凝藥物結(jié)合運(yùn)用I/A在未預(yù)先運(yùn)用GPb/a受體拮抗劑而方案進(jìn)展PCI的高?；颊?，建議在CAG后立刻便用阿昔單抗I/A，這種情況下依替巴肽或替羅非班的運(yùn)用價(jià)值較低a/B中高危的UA/NSTEMI患

13、者，建議在運(yùn)用口服抗血小板藥物的根底上，加用依替巴坦或替羅非班治療a/A 在CAG前的初始治療中運(yùn)用依替巴肽或替羅非班者，PCI術(shù)中和術(shù)后應(yīng)維持運(yùn)用原來(lái)的藥物a/B.2007年ACC/AHA/SCAI 關(guān)于UA/NSTEMI的PCI指南 UA/NSTEMI患者接受PCI術(shù)時(shí)，運(yùn)用靜脈GPb/a拮抗劑是有效的 (I/C)假設(shè)PCI術(shù)時(shí)給予氯吡格雷治療，同時(shí)結(jié)合運(yùn)用GPb/a 受體拮抗劑的抗血小板效果更好IIa/B對(duì)阿司匹林有絕對(duì)忌諱癥的患者，應(yīng)在PCI術(shù)前至少6小時(shí)給予300600mg負(fù)荷劑量的氯吡格雷；和/或PCI時(shí)給予GPb/a 受體拮抗劑(IIa/C).GPb/a受體拮抗劑在STEMI溶栓

14、中的運(yùn)用全劑量溶栓劑與GP b/a受體拮抗劑合用再灌注率提高，但出血風(fēng)險(xiǎn)明顯添加SPEED和GUSTO- Pilot實(shí)驗(yàn)顯示，Abciximab與半量t-PA合用，顯著提高梗死相關(guān)血管開(kāi)通率，但出血風(fēng)險(xiǎn)仍高于溶栓組.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受體拮抗劑在AMI患者PCI中的運(yùn)用.ACC/AHA 2007年關(guān)于STEMI的PCI指南對(duì)于已接受抗凝、擬行PCI的患者, 術(shù)前運(yùn)用UFH者，根據(jù)手術(shù)需求可予以UFH再次靜脈bolus,但同時(shí)應(yīng)思索GPb/a受體拮抗劑的協(xié)同抗凝效應(yīng) (I/C).G

16、PIIb/IIIa受體拮抗劑在PCI中的早期運(yùn)用 ELISA I 、EVEREST 、TIGER-PA、ONTIME 研討證明在PCI患者中，早期運(yùn)用急診室、監(jiān)護(hù)室或院前GPIIb/IIIa受體拮抗劑tirofiban效果優(yōu)于晚期運(yùn)用導(dǎo)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