非ST段抬高急性ACS的诊断治疗NSTEACS临床指南的解读

非ST段抬高急性ACS的诊断治疗NSTEACS临床指南的解读概况急性冠脉综合征图谱STElevationMINonSTElevationACSECG–ST

CK-MB

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

StableAnginaUnstableAnginaNon-QwaveMIQwaveMI急性冠脉综合征Presumedprognosis:veryhighriskofin-hospital

deathTreatmentgoal:preventdeathbyrestoringcoronarybloodflowFibrinolytic

therapyDirect

PCIPresumedprognosis:lowriskof

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

PCIManagemedicallyLow-

risk

featuresHigh-

risk

featuresACS患者6个月死亡率T-waveinversion

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

at6monthsSTMIwith

fibrinolyticsSTEMI&NSTEMI冠状动脉病变支数的比较SavonittoS,etal.JAmMedAsoc.1999;281:707-713.病因及病理急性冠脉综合征的病理机制易损斑块因破裂、侵蚀、钙化结节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%)的血栓阻塞状态取决于血栓形成的速度与体内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

血小板粘附于损伤的内皮表面并被激活

血小板内皮细胞内皮下腔血小板粘附到内皮下腔血小板血栓非ST段抬高的ACSResultsfromcross-linkingof

plateletsbyfibrinogenat

plateletreceptorsGPIIb-IIIa

atsiteofplaqueruptureplateletfibrinogenRuptured

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

lumenthrombusArterywallST段抬高AMIResultsfromstabilizationofa

plateletaggregateatsiteof

plaquerupturebyfibrinmeshplateletRBCfibrinmeshGPIIb-IIIa冠脉被血栓完全堵塞危险分层肌钙蛋白T对预后的影响:荟萃分析%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%白细胞计数和死亡率的关系CannonCP,etal.AmJCardiol.2001;87:636-639.(withpermission)肌钙蛋白I(TnI),C反应蛋白(CRP),

以及脑钠肽(BNP)水平与30天死亡率的关系P=.014P<.001671501557850471732490 SabatineM,etal.Circulation.2002;105:1760-1763.(withpermission)GUSTOIIb:ACS患者基础ECG改变与6个月死亡率的关系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积分评价年龄≥65years≥3冠心病危险因素继往冠心病史(狭窄>50%)7天内已服用阿斯匹林史≤24小时内心绞痛发作>2次ST改变心肌标志物升高

(CK-MBor肌钙蛋白)TIMI积分5-7，为高危病人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积分与死亡、心梗、急诊血管再建术复合终点的关系治疗－－基于循征医学的证据药物治疗早期介入治疗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的治疗目标病理生理改变治疗进程ACS(非阻塞性)斑块破裂血栓形成减少血栓负荷限制血栓进展促进斑块愈合和内环境稳定AMI(阻塞性)血栓性阻塞开通阻塞性血管限制损伤范围症状提示急性冠脉综合征评价12导联ECE慢性稳定性心绞痛可能ACS确定ACS药物治疗抗凝治疗

阻滞剂非心脏病诊断其它可疑疾病诊断评价再灌注症状提示急性冠脉综合征可疑ACS确诊ACSNSTEACSSTEACSECG无特异改变心肌标志物阴性ST-T改变胸痛持续心肌标志物阳性血流动力学不稳定观察、随访证实ACS收入院急性心肌缺血路经门诊随访UA/NSTEMI的急性期处理

抗缺血治疗吸氧、卧床、ECG监测硝酸酯类-阻滞剂ACEIUA,unstableangina;NSTEMI,non-ST-segmentelevationmyocardialinfarction;ECG,electrocardiogram;ACE,angiotensin-convertingenzyme.BraunwaldE,etal.JAmCollCardiol.2000;36:970-1062.抗栓治疗抗血小板治疗抗凝治疗

NSTEMI的药物治疗首选用药

抗缺血治疗

低分子肝素(LMWH)

阿司匹林/赛氯匹啶/氯比格雷次选用药

GPIIbIIIa阻滞剂替代治疗

凝血酶抑制剂其他

ACS的抗缺血治疗

Possible（可疑）

ACS阿斯匹林阿斯匹林+IV肝素Heparin+

GPIIb/IIIa拮抗剂高危或拟行介入治疗者氯吡格雷阿斯匹林+低分子肝素or静脉肝素Likely/Definite

（可能或确定）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推荐的抗栓治疗（I类指征）17.16.5*PlaceboASA05101520Patients(%)UnstableAngina

25.011.0*ASA01020303.31.9*ASA0123411.89.4*ASA051015AcuteMIAspirin在ACS中的应用*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氯吡格雷对阿斯匹林禁忌的患者，作为替代药物单独应用与阿斯匹林联用,改善急性期和远期预后介入治疗中应用

CURE PCICUREClopidogrel

+ASA*369Placebo

+ASA*MonthsofFollow-Up11.4%9.3%20%RRRP<0.001N=12,562012*IncombinationwithstandardtherapyTheCURETrialInvestigators.NEnglJMed.2001;345:494-502.一级终点事件-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–出血并发症50.00100200300400Daysoffollow-up12.6%8.8%31%RRRP=0.002

N=2658Clopidogrel+ASA*Placebo+ASA*CumulativeHazardRate*IncombinationwithstandardtherapyMehta,SR.etalfortheCURETrialInvestigators.Lancet.August2001.CompositeofcardiovasculardeathorMIfromrandomizationtoendoffollow-upPCI–CURE长期随访结果RR:Death/MIASAAlone68/655=10.4%Heparin+ASA55/698=7.9%BBBBBBB0.1110SummaryRelativeRisk0.67(0.44-0.1.02)TherouxRISCCohen1990ATACSHoldrightGurfinkel肝素的应用：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为首选治疗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普通肝素和依诺肝素的比较：

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

0.512OVERALLESSENCETIMI11BUFH

(%)Enox

(%)O.R.FavorsENOXFavors

UFHHeterogeneity:AllP=NS1.01.5严重出血事件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有关NSTE-ACS低分子肝素应用指南在应用阿斯匹林和/或氯吡格雷以外，应用皮下注射低分子肝素或静脉注射普通肝素抗凝Initialanticoagulationwithsubcut.LMWHorIVUFH,inadditiontoASA+/-clopidogrel

(ClassI;EvidenceA)凝血酶抑制剂的地位尚未确定，仍有待更多证据支持水蛭素BIVALIRUDIN血小板糖蛋白（GP）IIb/IIIa受体拮抗剂Abciximab阿昔单抗ReoproTirofiban替罗非班Eptifibatide依替巴肽Lamifiban拉米非班Xemilofiban珍米洛非班Sibrafiban西拉非班Orbofiban奥波非班Lefradafiban来达非班Integrelin引替瑞林Fradafiban夫雷非班GPIIbIIIa受体拮抗剂GPIIbIIIa受体拮抗剂改善ACS患者临床预后(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介入治疗中应用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早期介入治疗中应用GPIIbIIIaInhibitors的益处30天Death/MI/InterventionCombinationof

Aspirin,Thienopyridines,

GPIIbIIIaAntagonists&UH

联合应用阿斯匹林、噻氯匹定、GPIIbIIIa拮抗剂和普通肝素ESPRIT研究eptifibatide

180+180µg/kgbolus(boluses10minapart)

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

(ACT200-300sec)placebo+heparin60U/kgbolus

(ACT200-300sec)vs.试验设计ASA,thienopyridine<24°;randomizationincathlabelective(non-urgent)stentPCI48hour,30day,6month,1yearfollow-upprimaryendpoint:48°death,MI,urgentTVR,thromboticbailoutkeysecondaryendpoint(30d):death,MI,urgentTVRkeysecondaryendpoint(6m,1y):death,MI6个月时的死亡/MI事件P=0.001537%log-rankstatisticcumulativeeventrate(%)1年时死亡/MI/TVR24%RRRp=0.006822.1%17.5%cumulativeeventrate(%)months1年时糖尿病患者的TVR16.1%18.1%11.6%10.4%cumulativeeventrate(%)months=2.0%10%RRp=NS=1.2%11%RRp=NSCombinationof

LMWH&GPIIbIIIaInhibitors

inAcuteCoronarySyndrome

联合应用低分子肝素和

GPIIbIIIa拮抗剂INTERACT研究TheINTERACTStudy试验设计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小时内缺血事件UFHEnoxaparinP=0.000148-96HoursGoodmanetal,ACC2002n=346n=357n=320n=322UFHEnoxaparinP=0.083AllINTERACT30天严重出血事件UFHEnoxaparinP=0.079Non-CABGRelatedTIMIScale(LMWHtrials)Goodmanetal,ACC2002INTERACT:结论联合应用依替巴肽和依诺肝素较联合应用普通肝素可以：降低严重出血事件降低死亡及再发MI降低缺血发作Goodmanetal,ACC2002早期介入治疗？！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个月初级终点