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

血小板糖蛋白IIb/IIIa受體拮抗劑在介入/非介入患者中的應(yīng)用,浙江大學醫(yī)學院附屬第二醫(yī)院 心臟中心 王建安,基本原理 分子結(jié)構(gòu) 適應(yīng)癥和循證醫(yī)學 結(jié)論,血小板GPIIb/IIIa受體拮抗劑的作用機理,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,目前的GPIIb/IIIa受體拮抗劑依據(jù)化學結(jié)構(gòu)的不同可分為三類,1.單克隆抗體，Abciximab（阿昔單抗），最早應(yīng)用于臨床的GPIIb/IIIa受體拮抗劑，是GPIIb/IIIa受體的單克隆抗體，通過占據(jù)受體的位置而阻斷血小板聚集反應(yīng)。 2.肽類抑制劑，Eptifibatide（埃替非巴肽），是一類含有GPIIb/IIIa受體識別序列的低分子多肽。 3.非肽類抑制劑，靜脈的Tirofiban（替羅非班），是肽衍生物，其藥理性質(zhì)與埃替非巴肽相似。口服非肽類抑制劑，Xemilofiban、Orbofiban、Rocifiban、Sibrafiban、Lefradafiban、但試驗結(jié)果均以失敗告終。,三類 GPIIb/IIIa受體拮抗劑的化學結(jié)構(gòu),STEMI,Clinical finding,EKG,Serum markers,Risk assessment,Non-cardiac chest pain,Stable angina,UA,NSTEMI,Negative,Positive,ST-T wave changes,ST elevation,Low probability,Medium-high risk,Thrombolysis Primary PCI,Aspirin + GP IIb/IIIa inhibitor clopidogrel + heparin/ LMWH + anti-ischemic Rx Early invasive Rx,Discharge,Negative,Diagnostic rule out MI/ACS pathway,STEMI,Negative,Atypical pain,Low risk,Aspirin, heparin/low-molecular-weight heparin (LMWH) + clopidogrel Anti-ischemic Rx Early conservative therapy,Ongoing pain,DM=diabetes mellitus. Cannon, Braunwald. Heart Disease. 2001.,Rest pain, Post-MI, DM, Prior Aspirin,Exertional pain,The Spectrum of ACS,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 2002,0.5,0.6,0.7,1.1,Anti GPIIb/IIIa better,0.8,0.9,1.0,Relative 30-Day Risk of Death and MI,PRISM (3232) 7.1% 5.8% 0.80 0.60-1.06 PRISM-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 0.72-1.55 PURSUIT (10,948) 15.7% 14.2% 0.89 0.79-1.00 PARAGON-B (5225) 11.4% 10.6% 0.92 0.77-1.09 GUSTO-IV (7800) 8.0% (24h) 8.2% 1.02 0.83-1.24 (48h) 9.1% 1.15 0.94-1.39,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. 2002;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,Favors Control,Favors Treatment,Year,CAPTURE,1997,RESTORE,1998,EPISTENT,1999,1997,CADILLAC-P,2002,ADMIRAL,2001,RAPPORT,1998,Petronio,2002,CADILLAC-S,2002,0.01,0.1,1,10,100,Study,ERASER,1999,ISAR-2,2000,EPIC,Risk Ratio and 95% CI,RR 0.79 Z=-2.27 2P=0.023,EPILOG,1999,ESPRIT,2002,Overall,Tamburino,2002,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. 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 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,ACCP-7對NSTE ACS 治療建議：NSTE ACS的中、高?；颊咴缙谥委?，在應(yīng)用阿司匹林及肝素基礎(chǔ)上，加用Eptifibatide 或Tirofiban（1A級）；同時應(yīng)用氯吡格雷的中、高?；颊撸缙诩佑肊ptifibatide 或Tirofiban（2A級）。,急性冠狀動脈綜合征（ACS）中的應(yīng)用,ACC/AHA 2007年UA/NSTEMI指南,預(yù)行PCI的UA/NSTEMI患者，術(shù)前可應(yīng)用GPb/受體拮抗劑（I/A） 對可能行PCI的患者，阿昔單抗是上游GPb/a受體拮抗劑的首選藥物，否則依替巴肽或替羅非班是首選的藥物（I/B） UA/NSTEMI的高危患者行PCI，應(yīng)給予靜脈內(nèi)GPIIb/IIIa拮抗劑（ I/A ） 對于選擇保守策略的UA/NSTEMI患者，可應(yīng)用依替巴肽或替羅非班進行抗凝治療（b/B） 阿昔單抗不應(yīng)當應(yīng)用于不準備行PCI的患者（/A）,ESC 2007 年UA/NSTEMI指南,GPb/a受體拮抗劑應(yīng)該和抗凝藥物聯(lián)合應(yīng)用（I/A） 在未預(yù)先使用GPb/a受體拮抗劑而計劃進行PCI的高?；颊撸ㄗh在CAG后立即使用阿昔單抗（I/A），這種情況下依替巴肽或替羅非班的使用價值較低（a/B） 中高危的UA/NSTEMI患者，建議在使用口服抗血小板藥物的基礎(chǔ)上，加用依替巴坦或替羅非班治療（a/A） 在CAG前的初始治療中使用依替巴肽或替羅非班者，PCI術(shù)中和術(shù)后應(yīng)維持應(yīng)用原來的藥物（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，應(yīng)用靜脈GPb/a拮抗劑是有效的 (I/C) 如果PCI術(shù)時給予氯吡格雷治療，同時聯(lián)合應(yīng)用GPb/a 受體拮抗劑的抗血小板效果更好（IIa/B） 對阿司匹林有絕對禁忌癥的患者，應(yīng)在PCI術(shù)前至少6小時給予300600mg負荷劑量的氯吡格雷；和/或PCI時給予GPb/a 受體拮抗劑(IIa/C),GPb/a受體拮抗劑在STEMI溶栓中的應(yīng)用,全劑量溶栓劑與GP b/a受體拮抗劑合用再灌注率提高，但出血風險明顯增加 SPEED和GUSTO- Pilot試驗顯示，Abciximab與半量t-PA合用，顯著提高梗死相關(guān)血管開通率，但出血風險仍高于溶栓組,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 1999 ISAR-2 Neumann et al. (Stent) J Am Coll Cardiol 2000 ADMIRAL Montalescot et al (Stent) N Engl J Med, 2001 CADILLAC Stone et al. (Stent/PTCA) N Engl J Med, 2002 ACE Antoniucci et al. (Stent) J Am Coll Cardiol 2003 Pooled,Abciximab for PCI in AMI,0,0.5,1,1.5,GP IIb/IIIa受體拮抗劑在AMI患者PCI中的應(yīng)用,ACC/AHA 2007年關(guān)于 STEMI的PCI指南,對于已接受抗凝、擬行PCI的患者, 術(shù)前使用UFH者，根據(jù)手術(shù)需要可予以UFH再次靜脈bolus,但同時應(yīng)考慮GPb/a受體拮抗劑的協(xié)同抗凝效應(yīng) (I/C),GPIIb/IIIa受體拮抗劑在PCI中的早期應(yīng)用,ELISA I 、EVEREST 、TIGER-PA、ONTIME 研究證明在PCI患者中，早期應(yīng)用（急診室、監(jiān)護室或院前）GPIIb/IIIa受體拮抗劑（tirofiban）效果優(yōu)于晚期應(yīng)用（導管室）,ACC 2008：ON-TIME-2：Ongoing-Tirofiban In Myocardial Infarction Evaluation,Acute myocardial infarction diagnosed in ambulance or referral center ASA+600 mg Clopidogrel,Angiogram,Tirofiban *,Placebo,Transportation,PCI centre,Angiogram,Tirofiban provisional,Tirofiban contd,N=984 6/2006-11/2007,PCI,*Bolus: 25 g/kg & 0.15 g/kg/min infusion,Results: Primary Endpoint Residual ST deviation at 60 min,mean SD,Placebo,Tirofiban,p- value,Readable ECG,94.1%,95.5%,0.358,Residual,ST - deviation (mm),4.8 6.3,3.3 4.3,0.002, 3 mm ST-deviation,44.3%,36.6%,0.026,nor