血小板糖蛋白IIbIIIa受體拮抗劑在介入非介入患者中的應用

1、血小板糖蛋白iib/iiia受體拮抗劑在介入/非介入患者中的應用浙江大學醫(yī)學院附屬第二醫(yī)院 心臟中心王建安w基本原理w分子結構w適應癥和循證醫(yī)學w結論血小板gpiib/iiia受體拮抗劑的作用機理 mechanismwcompetitive antagonist of the gp receptor on the platelet surface for adhesive proteins such as fibrinogen, vwfwmaximally inhibit the final common pathway involved in platelet aggregation col

2、lagen adp thromboxane a2platelet activationplatelet aggregationthrombus formationgpiib/iiia inhibitoraspirinticlopidinclopidogrel目前的gpiib/iiia受體拮抗劑依據化學結構的不同可分為三類 1.單克隆抗體單克隆抗體，abciximab（阿昔單抗），最早應用于臨床的gpiib/iiia受體拮抗劑，是gpiib/iiia受體的單克隆抗體，通過占據受體的位置而阻斷血小板聚集反應。2.肽類抑制劑肽類抑制劑，eptifibatide（埃替非巴肽），是一類含有gpiib/i

3、iia受體識別序列的低分子多肽。3.非肽類抑制劑非肽類抑制劑，靜脈的tirofiban（替羅非班），是肽衍生物，其藥理性質與埃替非巴肽相似?？诜请念愐种苿瑇emilofiban、orbofiban、rocifiban、sibrafiban、lefradafiban、但試驗結果均以失敗告終。三類三類 gpiib/iiia受體拮抗劑的化學結構受體拮抗劑的化學結構stemiclinical findingekgserum markersrisk assessmentnon-cardiacchest painstableanginauansteminegativepositivest-t wave

4、 changesst elevationlowprobabilitymedium-high riskthrombolysisprimary 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 (

5、lmwh) + clopidogrelanti-ischemic rx early conservative therapyongoing paindm=diabetes mellitus.cannon, braunwald. heart disease. 2001.rest pain, post-mi, dm, prior aspirinexertional painthe spectrum of acsbenefit of gp iib/iiia blockade in acsmeta-analysis of six major trials (31,402 patients)all pa

6、tients with acspatients with acs, undergoing pci within 5 daysboersma e et al. lancet 2001.1anti gpiib/iiia betterrelative 30-day risk of death and miprism (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.

7、060.72-1.55pursuit (10,948)15.7%14.2% 0.890.79-1.00 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.

8、 2002;359:189-198.placebo bettergp iib/iiia betterodds ratio (95% ci)0.01.02.0study (n)gp iib/iiia inhibitors in ua/nstemi: death or mi at 30 daysfavors controlfavors treatmentyearcapture1997restore1998epistent19991997cadillac-p2002admiral2001rapport1998petronio2002cadillac-s20020.010.1110100studyer

9、aser1999isar-22000epicrisk ratio and 95% cirr 0.79z=-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 pcikong d, et al. a

10、m j cardiol. 2003; 92:651-655.placebo betteriib/iiia 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%

11、15,3391.3%cadillac 0.9%20,186odds ratio and 95% ci0.73 (0.55, 0.96)p=0.024meta-analysis of survival with platelet gp iib/iiia antagonists for pciwaccp-7對nste acs 治療建議：nste acs的中、高?；颊咴缙谥委?，在應用阿司匹林及肝素基礎上，加用eptifibatide 或tirofiban（1a級）；同時應用氯吡格雷的中、高?；颊?，早期加用eptifibatide 或tirofiban（2a級）。 急性冠狀動脈綜合征（acs）中的應用

12、acc/aha 2007年ua/nstemi指南w預行pci的ua/nstemi患者，術前可應用gpb/受體拮抗劑（i/a） w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） wua/nstemi的高危患者行pci，應給予靜脈內gpiib/iiia拮抗劑（ i/a ）w對于選擇保守策略的ua/nstemi患者，可應用依替巴肽或替羅非班進行抗凝治療（b/b）w阿昔單抗不應當應用于不準備行pci的患者（/a）esc 2007 年ua/nstemi指南wgpb/a受體拮抗劑應該和抗凝藥物聯(lián)合應用（i/a）w在未預先使用gpb/a受體拮

13、抗劑而計劃進行pci的高危患者，建議在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）w中高危的ua/nstemi患者，建議在使用口服抗血小板藥物的基礎上，加用依替巴坦或替羅非班治療（a/a） w在cag前的初始治療中使用依替巴肽或替羅非班者，pci術中和術后應維持應用原來的藥物（a/b）2007年acc/aha/scai 關于ua/nstemi的pci指南w ua/nstemi患者接受pci術時，應用靜脈gpb/a拮抗劑是有效的 (i/c)w如果pci術時給予氯吡格雷治療，同時聯(lián)合應用gpb/a 受體拮抗劑的抗血小板效果更好（iia/b）w對阿司匹林有

14、絕對禁忌癥的患者，應在pci術前至少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受體拮抗劑在受體拮抗劑在stemi溶栓中的應用溶栓中的應用w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wspeed和gusto- pilot試驗顯示，abciximab與半量t-pa合用，顯著提高梗死相關血管開通率，但出血風險仍高于溶栓組00.511.5relative risk of death+mi+tvrabciximab vs control30 days6 months rapport, brener et a

15、l.(ptca)circulation 1999isar-2neumann et al. (stent)j am coll cardiol 2000admiralmontalescot et al(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受體拮抗劑在受體拮抗劑在ami患者患者pci中的應用

16、中的應用acc/aha 2007年關于stemi的pci指南w對于已接受抗凝、擬行pci的患者, 術前使用ufh者，根據手術需要可予以ufh再次靜脈bolus,但同時應考慮gpb/a受體拮抗劑的協(xié)同抗凝效應 (i/c)gpiib/iiia受體拮抗劑在受體拮抗劑在pci中的中的早期應用應用 elisa i 、everest 、tiger-pa、ontime 研究證明在pci患者中，早期應用（急診室、監(jiān)護室或院前）gpiib/iiia受體拮抗劑（tirofiban）效果優(yōu)于晚期應用（導管室）acc 2008：on-time-2：ongoing-tirofiban in myocardial inf

17、arction evaluationtransportationpci centren=9846/2006-11/2007pci*bolus: 25 g/kg & 0.15 g/kg/min infusionmean sdplacebotirofibanp- valuereadable ecg94.1%95.5%0.358residualst - deviation (mm)4.8 6.33.3 4.30.002 3 mm st-deviation44.3%36.6%0.026normal ecg30.2%37.3%0.031residual st 3 mm (combined)pla

18、cebo bettertirofiban betterall patients (pci)male genderfemale genderdiabetesno diabetestimi risk 3timi risk 3age median value0.1110primary endpointsubgroupsevent-free survivaltime (days)302520151050event free survival90%80%70%60%50%40%tirofibanplacebop value 0,012ongoing tirofiban in myocardial infaction evaluationp