非ST段抬高急性ACS的診斷治療NSTEACS臨床指南的解讀

非ST段抬高急性ACS的診斷治療NSTEACS臨床指南的解讀概況急性冠脈綜合征圖譜STElevationMINonSTElevationACSECG–ST

CK-MB

TroponinCRP,IL-6,TNFa,PAI1,NF-KB,CD40,COX-2ECG-ST

StableAnginaUnstableAnginaNon-QwaveMIQwaveMI急性冠脈綜合征Presumedprognosis:veryhighriskofin-hospital

deathTreatmentgoal:preventdeathbyrestoringcoronarybloodflowFibrinolytic

therapyDirect

PCIPresumedprognosis:lowriskof

in-hospitaldeath,unlessMIdevelopsTreatmentgoal:stabilizewithaspirinheparin&monitorforMIdevelopment+Cardiacenzymes–CardiacEnzymesScheduled

PCIManagemedicallyLow-

risk

featuresHigh-

risk

featuresACS患者6個(gè)月死亡率T-waveinversion

ACSSTACSGrangerCBetal.JAmCollCardiol.1998;31:79A.%Cumulativemortality

at6monthsSTMIwith

fibrinolyticsSTEMI&NSTEMI冠狀動(dòng)脈病變支數(shù)的比較SavonittoS,etal.JAmMedAsoc.1999;281:707-713.病因及病理急性冠脈綜合征的病理機(jī)制易損斑塊因破裂、侵蝕、鈣化結(jié)節(jié)等因素引起血栓形成血栓形成可以形成阻塞性(15%)或非阻塞性(85%)的血栓阻塞狀態(tài)取決于血栓形成的速度與體內(nèi)自溶的平衡血小板聚集形成血栓

血小板的粘附和激活

血流中的正常血小板

血小板粘附于損傷的內(nèi)皮表面并被激活

血小板內(nèi)皮細(xì)胞內(nèi)皮下腔血小板粘附到內(nèi)皮下腔血小板血栓非ST段抬高的ACSResultsfromcross-linkingof

plateletsbyfibrinogenat

plateletreceptorsGPIIb-IIIa

atsiteofplaqueruptureplateletfibrinogenRuptured

plaqueGPIIb-IIIa冠脈被富含血小板的血栓部分堵塞Unobstructed

lumenthrombusArterywallST段抬高AMIResultsfromstabilizationofa

plateletaggregateatsiteof

plaquerupturebyfibrinmeshplateletRBCfibrinmeshGPIIb-IIIa冠脈被血栓完全堵塞危險(xiǎn)分層肌鈣蛋白T對(duì)預(yù)后的影響:薈萃分析%RR3.9

(2.9-5.3)RR3.8

(2.6-5.5)No.Studies: 13 6Neg

Pos(TropI+T)36341849737322HeidenreichPA,JAmCollCardiol.2001;38:478-485.WBCCount(x103)30-DayMortality0510152005%10%15%20%白細(xì)胞計(jì)數(shù)和死亡率的關(guān)系CannonCP,etal.AmJCardiol.2001;87:636-639.(withpermission)肌鈣蛋白I(TnI),C反應(yīng)蛋白(CRP),

以及腦鈉肽(BNP)水平與30天死亡率的關(guān)系P=.014P<.001671501557850471732490 SabatineM,etal.Circulation.2002;105:1760-1763.(withpermission)GUSTOIIb:ACS患者基礎(chǔ)ECG改變與6個(gè)月死亡率的關(guān)系CumulativeMortality

(%)02468100306090120150180DaysFromRandomizationT-waveinversionSTACSSTEMIwith

fibrinolyticsGUSTO,GlobalUseofStrategiesToOpenOccludedArteriesinAcuteCoronarySyndromes;ECG,electrocardiogram;ACS,acutecoronarysyndrome;STEMI,ST-segmentelevationmyocardialinfarction.

SavonittoS,etal.JAMA.1999;281:707-713.(withpermission)TIMI,thrombosisinmyocardialinfarction;UA,unstableangina;NSTEMI,non–ST-segmentelevationmyocardialinfarction;CAD,coronaryarterydisease.

AntmanEM,etal.JAMA.2000;284:835-842.非ST段抬高ACS的TIMI積分評(píng)價(jià)年齡≥65years≥3冠心病危險(xiǎn)因素繼往冠心病史(狹窄>50%)7天內(nèi)已服用阿斯匹林史≤24小時(shí)內(nèi)心絞痛發(fā)作>2次ST改變心肌標(biāo)志物升高

(CK-MBor肌鈣蛋白)TIMI積分5-7，為高危病人AntmanEM,etal.JAMA.2000;284:835-442.(withpermission)Population(%):4.78.313.219.926.240.9010203040500/123456/7D/MI/UrgRevasc(%)NumberofRiskFactors4.317.332.029.313.03.4CStatistic=0.65c2trendP<.001TIMI積分與死亡、心梗、急診血管再建術(shù)復(fù)合終點(diǎn)的關(guān)系治療－－基于循征醫(yī)學(xué)的證據(jù)藥物治療早期介入治療Vascular

DamageInflammationMyocyteNecrosisAcceleratedAtherosclerosisHemodynamicStressHbA1cBlood

glucoseCrClMicroalbuminuriaTroponinBNP,NT-proBNPhs-CRP,CD40LMorrowDA,etal.Circulation.2003;108:250-252.MultimarkerStrategyinACSAge653CADriskfactors(FHx,HTN,chol,DM,activesmoker)STdeviation0.5mmcardiacmarkersRecent(24H)severeanginaHISTORICALPRESENTATIONRISKSCORE=TotalPoints(0-7)KnownCAD(stenosis50%)ASAuseinpast7days0/123456/7RISKSCORERISKOFCARDIACEVENTS(%)BY14DAYSINTIMI11B*33571219AntmanetalJAMA2000;284:835-8421111111TIMIRISKSCOREforUA/NSTEMIPOINTSDEATHORMIDEATH,MIORURGENTREVASC5813202641*Entrycriteria:UAorNSTEMIIdefinedasischemicpainatrestwithinpast24H,withevidenceofCAD(STsegmentdeviationor+marker)ACS的治療目標(biāo)病理生理改變治療進(jìn)程ACS(非阻塞性)斑塊破裂血栓形成減少血栓負(fù)荷限制血栓進(jìn)展促進(jìn)斑塊愈合和內(nèi)環(huán)境穩(wěn)定AMI(阻塞性)血栓性阻塞開通阻塞性血管限制損傷范圍癥狀提示急性冠脈綜合征評(píng)價(jià)12導(dǎo)聯(lián)ECE慢性穩(wěn)定性心絞痛可能ACS確定ACS藥物治療抗凝治療

阻滯劑非心臟病診斷其它可疑疾病診斷評(píng)價(jià)再灌注癥狀提示急性冠脈綜合征可疑ACS確診ACSNSTEACSSTEACSECG無特異改變心肌標(biāo)志物陰性ST-T改變胸痛持續(xù)心肌標(biāo)志物陽性血流動(dòng)力學(xué)不穩(wěn)定觀察、隨訪證實(shí)ACS收入院急性心肌缺血路經(jīng)門診隨訪UA/NSTEMI的急性期處理

抗缺血治療吸氧、臥床、ECG監(jiān)測(cè)硝酸酯類-阻滯劑ACEIUA,unstableangina;NSTEMI,non-ST-segmentelevationmyocardialinfarction;ECG,electrocardiogram;ACE,angiotensin-convertingenzyme.BraunwaldE,etal.JAmCollCardiol.2000;36:970-1062.抗栓治療抗血小板治療抗凝治療

NSTEMI的藥物治療首選用藥

抗缺血治療

低分子肝素(LMWH)

阿司匹林/賽氯匹啶/氯比格雷次選用藥

GPIIbIIIa阻滯劑替代治療

凝血酶抑制劑其他

ACS的抗缺血治療

Possible（可疑）

ACS阿斯匹林阿斯匹林+IV肝素Heparin+

GPIIb/IIIa拮抗劑高危或擬行介入治療者氯吡格雷阿斯匹林+低分子肝素or靜脈肝素Likely/Definite

（可能或確定）ACS氯吡格雷* ClassIIa:enoxaparinpreferredoverUFHunlessCABGplannedwithin24hours.

ACC,AmericanCollegeofCardiology;AHA,AmericanHeartassociation;ACS,acutecoronary syndrome;PCI,percutaneouscoronaryintervention;SQLMWH,subcutaneouslowmolecular-weight heparin;IV,intravenous.

BraunwaldE,etal.JAmCollCardiol.2000;36:970-1062.ACC/AHA推薦的抗栓治療（I類指征）17.16.5*PlaceboASA05101520Patients(%)UnstableAngina

25.011.0*ASA01020303.31.9*ASA0123411.89.4*ASA051015AcuteMIAspirin在ACS中的應(yīng)用*P<.0001DeathorMI*P=.003Reocclusion*P=.012MI*P<.001DeathN= 397 399 513 419 8587 8600 8587 8600MI,myocardialinfarction;ASA,acetylsalicylicacid;RISC,ResearchonInStabilityinCoronaryarterydisease.RISCGroup.Lancet.1990;336:827-830.RouxS,etal.JAmCollCardiol.1992;19:671-677.ISIS-2.Lancet.1988;2:349-360.PlaceboPlaceboPlacebo氯吡格雷對(duì)阿斯匹林禁忌的患者，作為替代藥物單獨(dú)應(yīng)用與阿斯匹林聯(lián)用,改善急性期和遠(yuǎn)期預(yù)后介入治療中應(yīng)用

CURE PCICUREClopidogrel

+ASA*369Placebo

+ASA*MonthsofFollow-Up11.4%9.3%20%RRRP<0.001N=12,562012*IncombinationwithstandardtherapyTheCURETrialInvestigators.NEnglJMed.2001;345:494-502.一級(jí)終點(diǎn)事件-MI/Stroke/CVDeathPlacebo

+ASA*

N=6303Clopidogrel+ASA*

N=6259Majorbleeding 2.7% 3.7%**

Life-threateningbleeding 1.8% 2.2%?

Non-life-threateningbleeding 0.9% 1.5%?

Minorbleeding 2.4% 5.1%§EndPoint*Incombinationwithstandardtherapy**P=0.001;?

P=NS;?

P

=0.002;§P<0.001.TheCURETrialInvestigators.NEnglJMed.2001;345:494-502.CURE–出血并發(fā)癥50.00100200300400Daysoffollow-up12.6%8.8%31%RRRP=0.002

N=2658Clopidogrel+ASA*Placebo+ASA*CumulativeHazardRate*IncombinationwithstandardtherapyMehta,SR.etalfortheCURETrialInvestigators.Lancet.August2001.CompositeofcardiovasculardeathorMIfromrandomizationtoendoffollow-upPCI–CURE長(zhǎng)期隨訪結(jié)果RR:Death/MIASAAlone68/655=10.4%Heparin+ASA55/698=7.9%BBBBBBB0.1110SummaryRelativeRisk0.67(0.44-0.1.02)TherouxRISCCohen1990ATACSHoldrightGurfinkel肝素的應(yīng)用：ComparisonofHeparin+ASAvsASAAloneASA,acetylsalicylicacid;RISC,ResearchonInStabilityinCoronaryarterydisease;ATACS,AntithromboticTherapyinAcuteCompanySyndromes;RR,relativerisk;MI,myocardialinfarction.OlerA,etal.JAMA.1996;276:811-815.(withpermission)低分子肝素（LMWH）LMWHismorereliable&willprobablyreplaceUFHasprimarytherapy,withattentiontoincreasedbleedingrisk低分子肝素可替代普通肝素作為首選治療BetterOutcome

OR

BetterPatencyFRAXIS 0.93 ASSENT-PlusTIMI11B 0.85 AMI-SKESSENCE 0.80 HART-2

0123456789081624324048566472%PtsHoursfromRandomizationUFHENOX5.2%4.2%RRR18%P=0.217.3%5.5%RRR24%P=0.03ESSENCETIMI11B普通肝素和依諾肝素的比較：

TIMI11BvsESSENCE：Death/MI/UrgentRevasc.AntmanEMetal,Circulation1999Oct12;100(15):1602-8

0.512OVERALLESSENCETIMI11BUFH

(%)Enox

(%)O.R.FavorsENOXFavors

UFHHeterogeneity:AllP=NS1.01.5嚴(yán)重出血事件1.3OR

(95CI)

P1.52

(0.86-2.69)NS0.91

(0.47-1.78)NS1.23

(0.80-1.89)NSAntmanEMetal,Circulation1999Oct12;100(15):1602-8ACC/AHA有關(guān)NSTE-ACS低分子肝素應(yīng)用指南在應(yīng)用阿斯匹林和/或氯吡格雷以外，應(yīng)用皮下注射低分子肝素或靜脈注射普通肝素抗凝Initialanticoagulationwithsubcut.LMWHorIVUFH,inadditiontoASA+/-clopidogrel

(ClassI;EvidenceA)凝血酶抑制劑的地位尚未確定，仍有待更多證據(jù)支持水蛭素BIVALIRUDIN血小板糖蛋白（GP）IIb/IIIa受體拮抗劑Abciximab阿昔單抗ReoproTirofiban替羅非班Eptifibatide依替巴肽Lamifiban拉米非班Xemilofiban珍米洛非班Sibrafiban西拉非班Orbofiban奧波非班Lefradafiban來達(dá)非班Integrelin引替瑞林Fradafiban夫雷非班GPIIbIIIa受體拮抗劑GPIIbIIIa受體拮抗劑改善ACS患者臨床預(yù)后(Death&MIrate)(4Pstudies)Study

N

OR

GPIIbIIIaI

Placebo

PPRISM+7d1915 0.58 4.9% 8.3% 0.006PRISM+30d1915 0.73 8.7% 11.9% 0.03PURSUIT7d10946 0.89 10.1% 11.6% 0.02PURSUIT30d10946 0.92 14.2% 15.7% 0.04PARAGONA2282 0.89 10.3% 11.7% 0.48PARAGONB5220 0.90 10.6% 11.5%0.32GPIIbIIIaInhibitorsACS介入治療中應(yīng)用EPIC 2099

Abciximab 8.312.8EPILOG 2792

Abciximab 5.311.7EPISTENT 1603

Abciximab 5.310.8

(stentarmsonly)IMPACT-II

4010Eptifibatid9.511.4ESPRIT 2064

Eptifibatide6.810.4RESTORE 2141

Tirofiban 8.010.5 OddsRatioTrial N Agent IIb/IIIa Control (95%CI)30-DayDeath,MI,UrgentRevascularization%0.00.51.02.0PresentedatAHAScientificSessionsNov.15,2000早期介入治療中應(yīng)用GPIIbIIIaInhibitors的益處30天Death/MI/InterventionCombinationof

Aspirin,Thienopyridines,

GPIIbIIIaAntagonists&UH

聯(lián)合應(yīng)用阿斯匹林、噻氯匹定、GPIIbIIIa拮抗劑和普通肝素ESPRIT研究eptifibatide

180+180μg/kgbolus(boluses10minapart)

2.0μg/kg-mininfusionx18-24°+heparin60U/kgbolus

(ACT200-300sec)placebo+heparin60U/kgbolus

(ACT200-300sec)vs.試驗(yàn)設(shè)計(jì)ASA,thienopyridine<24°;randomizationincathlabelective(non-urgent)stentPCI48hour,30day,6month,1yearfollow-upprimaryendpoint:48°death,MI,urgentTVR,thromboticbailoutkeysecondaryendpoint(30d):death,MI,urgentTVRkeysecondaryendpoint(6m,1y):death,MI6個(gè)月時(shí)的死亡/MI事件P=0.001537%log-rankstatisticcumulativeeventrate(%)1年時(shí)死亡/MI/TVR24%RRRp=0.006822.1%17.5%cumulativeeventrate(%)months1年時(shí)糖尿病患者的TVR16.1%18.1%11.6%10.4%cumulativeeventrate(%)months=2.0%10%RRp=NS=1.2%11%RRp=NSCombinationof

LMWH&GPIIbIIIaInhibitors

inAcuteCoronarySyndrome

聯(lián)合應(yīng)用低分子肝素和

GPIIbIIIa拮抗劑INTERACT研究TheINTERACTStudy試驗(yàn)設(shè)計(jì)746patientsUA/NSTEMIChestpain>10minwithin24hr0.5mmSTSegmentdepression/transientelevationPositivecardiacmarkers(CK-MBortroponin)180/2.0doseeptifibatidefor48hrsASA160mginitially80-325mgdailyTreatmentGroupAUFH70IU/kgbolus/0.15U/kg-hr(aPTT50-70sec)(n=366)TreatmentGroupB1.0mg/kgq12enoxaparin(n=380)Endpoints:Primary-Major/MinorTIMIBleedingSecondary-D/MI/recurrentischemia

-STsegmentmonitoringGoodmanetal,ACC2002UFHEnoxaparinP=0.00020-48HoursINTERACT:96小時(shí)內(nèi)缺血事件UFHEnoxaparinP=0.000148-96HoursGoodmanetal,ACC2002n=346n=357n=320n=322UFHEnoxaparinP=0.083AllINTERACT30天嚴(yán)重出血事件UFHEnoxaparinP=0.079Non-CABGRelatedTIMIScale(LMWHtrials)Goodmanetal,ACC2002INTERACT:結(jié)論聯(lián)合應(yīng)用依替巴肽和依諾肝素較聯(lián)合應(yīng)用普通肝素可以：降低嚴(yán)重出血事件降低死亡及再發(fā)MI降低缺血發(fā)作Goodmanetal,ACC2002早期介入治療？！VANQWISHTrialVAHospitalsStudy:ManagementpostNon-QwaveMIBodenWE:PresentedattheACCScientificSessions1997,AnaheimCACombinedEndpointDeathRatesNon-fatalMIRatesPercent0510152025005101551015Discharge12moInvasiveConservativeDischarge12moDischarge12mop=0.004p=0.05p=0.007p=0.025DeathorMIP=NS12.2%10.8%EarlyConservativeEarlyInvasiveWeeksAndersonHVetal.,JACC1995;26:1643-1650.TIMIIIIBOneYearResultsFRISCII-DeathorMIat6monthsPatientsEligibleforRevascularizationLancet1999;354:708-15p=0.031Table3.TACTICS-CardiacEventsat30days

0123456Time(months)048121620%PatientsCONSINVO.R0.7895%CI(0.62,0.97)p=0.02519.4%15.9%TACTICS-TIMI18研究6個(gè)月初級(jí)終點(diǎn)