血小板糖蛋白iibiiia受体拮抗剂在介入非介入患者中的应用.pptxVIP

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基本原理分子结构适应症和循证医学结论血小板GPIIb/IIIa受体拮抗剂的作用机理 Collagen ADP Thromboxane A2Platelet Activationplatelet aggregationThrombus formation 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 aggregationAspirinCOXTiclopidinClopidogrelGPIIb/IIIa inhibitor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。三类 GPIIb/IIIa受体拮抗剂的化学结构The Spectrum of ACSNon-cardiacchest painStableanginaNSTEMISTEMIUAAtypical painExertional painRest pain, Post-MI, DM, Prior AspirinOngoing painClinical finding NegativeST-T wave changesST elevationEKGNegativePositiveSerum markersLowprobabilityLow riskMedium-high riskSTEMIRisk assessmentDiagnostic rule out MI/ACS pathwayAspirin, heparin/low-molecular-weight heparin (LMWH) + clopidogrelAnti-ischemic Rx Early conservative therapyThrombolysisPrimary PCINegativeAspirin + GP IIb/IIIa inhibitor clopidogrel + heparin/LMWH + anti-ischemic RxEarly invasive RxDischargeDM=diabetes mellitus.Cannon, Braunwald. Heart Disease. 2001.Benefit of GP IIb/IIIa Blockade in ACSMeta-Analysis of Six Major Trials (31,402 Patients)Relative 30-Day Risk of Death and MIAll patients with ACSPatients with ACS, undergoing PCI within 5 days0.50.60.70.80.91.01.1Anti GPIIb/IIIa betterBoersma E et al. Lancet 2002GP IIb/IIIa Inhibitors in UA/NSTEMI: Death or MI at 30 DaysOdds Ratio95% CIStudy (n)PlaceboIV GP IIb/IIIaPRISM (3232) 7.1% 5.8%? 0.80 0.60-1.06PRISM-PLUS (1915) 12.0% 8.7% 0.70 0.50-0.98 PARAGON-A (2282) 11.7% (l) 10.3% 0.87 0.58-1.29 (h) 12.3% 1.06 0.72-1.55PURSUIT (10,948) 15.7% 14.2% 0.89 0.79-1.00 PARAGON-B (5225) 11.4% 10.6%