非ST段抬高急性冠脈綜合征介入治療

-策略與選擇

阜外心血管病醫(yī)院

喬樹賓

ACS住院患者（NSTE-ACS

vs

STEMI）NationalCenterforHealthStatistics.2001.ACS2.3millionhospitaladmissionsACS

(230萬/年ACS住院患者）UA/NSTEMI1.43millionadmissionsperyear（143萬/年患者占63%）STEMI829,000

admissionsperyear（82.9萬/年患者占36%）ACS主要發(fā)病機(jī)理動(dòng)脈粥樣硬化斑塊--不穩(wěn)定或破裂血栓形成炎癥細(xì)胞少量平滑肌細(xì)胞激活的巨噬細(xì)胞血栓ACS的病理生理基礎(chǔ)CK-MBorTroponinTroponinelevatedornotAdaptedfromMichaelDaviesAdaptedfromMichaelDavies

ACS無持續(xù)ST段抬高

ACS伴持續(xù)ST段抬高ACS的臨床分型ACSST段持續(xù)抬高的ACS無ST段抬高的ACScTnT(cTnI)≥0.1μg/L或CK-MB≥正常上限的2倍cTnT(cTnI)＜0.1μg/L

或CK-MB<正常上限的2倍STEMINSTEMI

UA非ST段抬高ACS的治療

抗血小板治療抗凝治療抗缺血治療調(diào)脂治療

介入治療冠脈搭橋抗栓—不溶栓抗血小板、抗凝PCI？！診斷常規(guī)血生化，特別包括TnT或I監(jiān)測心電ST段的變化超聲心動(dòng)圖檢查如需排除主動(dòng)脈夾層，做MRI；

排除肺栓塞行CT或核素檢查觀察對(duì)抗缺血治療的效果評(píng)定危險(xiǎn)記分評(píng)價(jià)出血的危險(xiǎn)性NSTE-ACS危險(xiǎn)分層臨床因素年齡原有基礎(chǔ)的左室功能冠脈解剖糖尿病及腎肺功能異常等其它合并病心絞痛的病史特點(diǎn)

心電圖或動(dòng)態(tài)心電圖

心肌缺血的表現(xiàn)

ST段和T波改變

肌鈣蛋白Ｃ反應(yīng)蛋白纖維蛋白肽ＡBNP

或NTproBNP

NSTE-ACS危險(xiǎn)分層方法

----早期CAG的價(jià)值早期冠脈造影目的：

病變范圍和分布、狹窄程度和部位、適合何種血管重建術(shù)等。早期冠脈造影------提高預(yù)后分層的可靠性------確定治療方案的有效方法：

①?zèng)]有病變可迅速出院②罪犯病變適合PCI者可立即介入治療加快出院③左主干病變、復(fù)雜病變伴左室功能不全者迅速CABG

------發(fā)現(xiàn)高危病人，使患者從早期血管重建術(shù)中獲益ACC/AHA：治療的選擇（一）有創(chuàng)治療：1.盡管充分藥物治療仍發(fā)生靜息或低水平活動(dòng)心絞痛；2.TnT或TnI升高；3.新出現(xiàn)的ST壓低；4.HF體征和癥狀或新出現(xiàn)或加重的二尖瓣返流；5.無創(chuàng)檢查有高危的證據(jù)；6.持續(xù)性室速；7.六個(gè)月內(nèi)曾PCI；8.先前CABG；9.危險(xiǎn)積分屬高危（TIMI，GRACE）；10.左心室功能降低（LVEF<40%）ACC/AHA：治療的選擇（二）保守治療：計(jì)分屬低危險(xiǎn)（TIMI，GRACE）無高危特征的患者或醫(yī)生選擇2007-ESC介入治療緊急（Urgent）1.患者出現(xiàn)持續(xù)性或反復(fù)胸痛，伴有或不伴有ST改變（≥2mm）或深的倒置T波，抗缺血治療效果不好2.出現(xiàn)心衰臨床癥狀或血流動(dòng)力學(xué)不穩(wěn)定3.致命性心律失常（VF、VT）早期<72小時(shí)1.TnT或I↑2.動(dòng)態(tài)ST或T改變（有癥狀或無癥狀）3.糖尿病4.腎功能異常（GFR<60ml/min/1.73m2）5.左心室功能降低（LVEF<40%）6.梗塞后心絞痛7.有MI病史8.6個(gè)月內(nèi)行PCI,有CABG史9.中高GRACE危險(xiǎn)記分不做或擇期做無再發(fā)胸痛無心衰的體征無新的ECG改變（就診6-12小時(shí)）TnT或I正常（就診6-12小時(shí)）0.20.5125FavorsInvasiveFavorsConservativeOddsRatioDeathorMIOR0.82,P=0.001TrialTIMI3BVANQWISHMATEFRISCIITACTICSRITA3TOTALMehtaSRetal.JAMA2005;293:2908-175.1%8.1%27.2%28.0%12.0%8.9%4.3%11.4%4.0%5.3%7.4%10.9%VINO4.8%14.8%InvCons7.4%11.0%InvasiveManagementofUA/NSTEMI

Meta-analysis:Death/MIat17mo.F/UOverall12.214.4Trials<1999*19.319.6Trials>1999?9.412.4Troponin+ve10.014.0Troponin–ve6.77.4AnyMarker+ve14.717.4AnyMarker-ve7.78.5FavorsInvasiveFavorsConservative0.512TrialInv(%)Cons(%)OddsRatioPvalue0.0010.820.400.900.0120.820.420.890.0010.690.00010.730.920.99*TIMI3B,VANQWISHandMATE?FRISCII,TACTICS,VINO,RITA3DatabytroponinstatusavailableonlyinFRISCII,TACTICS,RITA3InvasiveManagementofUA/NSTEMIMeta-analysis:SubgroupsMehtaSRetal.JAMA2005;293:2908-17DeathorMIatFollowup36018090300ProbabilityofDeath.04.03.02.010Non-Invasive(n=1235)Invasive(n=1222) Invasive Noninvasive RR(95%CI) 2.2% 4.0% 0.56(0.35-0.89)p=0.018Wallentin,Lancet2000FRISC-IIMortalityatOne-Year

InvasiveVs.ConservativeManagementStrategies

FRISCII:5YearOutcomesEndpointInvasive

strategy(%)Noninvasivestrategy(%)Relativerisk

(95%CI)DeathorMI19.924.50.81

(0.69–0.95)All-causemortality9.710.10.95

(0.75–1.21)MI12.917.70.73

(0.60–0.89)LagerqvistB.WorldCongressofCardiology2006;September4,2006,Barcelona,Spain.FRISCII:5YearOutcomesDeathorMIat5yearsinhigh-,medium-,andlow-riskpatientsEndpointInvasive

strategy(%)Noninvasivestrategy(%)Relativerisk

(95%CI)DeathorMIin

high-riskpatients(FRISC4–7)32.741.60.79

(0.64–0.97)DeathorMIinmedium-riskpatients(FRISC2–3)14.620.40.72(0.55–1.13)DeathorMIinlow-riskpatients(FRISC0–1)6(0.66–2.40)LagerqvistB.WorldCongressofCardiology2006;September4,2006,Barcelona,Spain.哪種治療最好？

（Invasive

vs

Conservative）Conservative（保守）

920PatientsInvasive（介入）

7,018PatientsTIMIIIIBVANQWISHMATEFRISCIITACTICS-

TIMI18VINORITA-3

TRUCS

ISAR-COOLAdaptedfromCannonCP.Cardiology.2002;8(specialedition):29-37.Conservative

1,674PatientsRoutinevsSelectiveInvasive

StrategiesinACSAdaptedfromMehtaS,etal.JAMA.2005;293;2908-2917.OddsRatio(95%CI)0.11.0OR-0.8295%CI,0.72-0.93P<0.001Total 561/4608(12.2) 663/4604(14.4)CompositeofDeathorMyocardialInfarctionNo./Total(%)FavorsRoutineInvasiveFavorsSelectiveInvasiveSourceRoutineInvasiveSelectiveInvasiveTIMIIIIB 86/740(11.6)101/733(13.8)VANQWISH152/462(32.9)139/458(30.3)MATE16/111(14.4)11/90(12.2)FRISCII127/1222(10.4)174/1235(14.1)TACTICS81/1114(7.3)105/1106(9.5)VINO4/64(6.3)15/67(22.4)RITA395/895(10.6)118/915(12.9)10StudyMortalityduringhospitalizationMortalityafterdischargeCons(%)Inv(%)OddsRatio,95%CITIMI3B0.20.512510FavorsRoutineFavorsSelectiveVANQWISH11.713.4MATE6.910.0FRISCII3.01.2TACTICS2.81.9VINO9.41.6RITA37.35.2Subtotal1.11.8TIMI3B1.92.2VANQWISH1.34.5MATE3.30.9FRISCII0.91.1TACTICS0.71.4VINO4.51.6RITA30.71.6Subtotal3.84.9MehtaSRetal.JAMA2005;293:2908-17OR1.60,P=0.007OR0.76,P=0.01InvasiveRxinACS:EarlyandLateMortalityCRUSADE:

InvasiveCardiacProceduresintheUSProceduresPerformed(non-transfer)DiagnosticCath 64%

—Within48hours 41%—Within24hours 27%PercutaneousIntervention 35%

—Within48hours 25%CoronaryBypassGrafting 11%AnInternationalRandomizedTrialofEarlyVersusDelayedInvasiveStrategiesinPatientswithNon-STSegmentElevationAcuteCoronarySyndromesFUNDEDBYTHECANADIANINSTITUTESOFHEALTHRESEARCHGrant#

150904TIMACS

TimingofIntervention

inpatientswith

AcuteCoronarySyndromes

StudyObjective

Todeterminewhetherearlyinterventionissuperiortodelayedinterventioninpatientswithhighrisknon-STsegmentelevationacutecoronarysyndromeDesign,EligibilityCriteriaandProtocolUAorNSTEMI2of3Criteria:Age>60,ischemicEKGΔor↑biomarkerANDsuitableforrevascularizationRANDOMIZE*EarlyInvasiveCoronaryangiographyassoonaspossible(nolaterthan24hours)followedbyPCIorCABGDelayedInvasiveCoronaryangiography

anytime>36hrsfollowedbyPCIorCABGASA,clopidogrel,GPIIb/IIIaantagonistasperroutinepractice*Centerchoserandomizationratio1:1,1:2or2:1Early:DelayedExcludedContraindicationforLMWHorhighriskofbleedingornotasuitablecandidateforrevascularizationFollow-upat30daysand6monthsOutcomesPrimaryCompositeofDeath,newMIorStrokeat6mo.SecondaryCompositeof:Death,newMIorrefractoryischemiaDeath,newMI,stroke,refractoryischemiaorrepeatrevascularizationStrokeStudyFlowChartTIMACSStandAloneN=1,398TIMACSTotalN=3,031TIMACSOASIS5N=1,633+30Dayand6monthFollow-up3,029LosttoFollow-up:4RecommendedMedicalTreatmentASA,clopidogrelGPIIb/IIIainhibitoratdiscretionofattendingphysician(especiallyifptisnotonathienopyridine)Antithrombin:

OASIS5:Eitherfondaparinuxorenoxaparin

TIMACSstandalone:UFHorLMWHorfondaparinuxorbivalirudin(investigatordiscretion)BetablockerStatinParticipatingCountriesNorthAmerica650SouthAmerica442Europe1065Asia846Australia28TIMACSSteeringCommitteeA.Avezum–BrazilC.Morillo--ColumbiaJ-P.Bassand–FranceL.Piegas–BrazilW.Boden–USAJ.Probstfield–USAJ.Col–BelgiumS.Qiao--ChinaR.Diaz–ArgentinaH-JRupprecht–GermanyD.Faxon–USAP.G.Steg–FranceC.Granger–USAJ-F.Tanguay--CanadaC.Joyner--CanadaP.Widimsky–CzechRepM.Kenda–SloveniaJ.Varigos–AustraliaS.Mehta--CanadaS.Yusuf--CanadaT.Moccetti–SwitzerlandJ.Zhu–ChinaStudyOrganizationCoordinatingCenter:PHRI,McMasterUniversityS.Mehta,S.Yusuf,S.Jolly,C.Horsman,S.Chrolavicius,B.MeeksDSMB:P.Sleight(chair),J.Anderson,D.DeMets,D.Johnstone,D.HolmesAdjudicationCommitteeChair:C.Joyner Coordinator:M.LawrenceCriteriaforCrossoverfromDelayedGrouptoEarlyGroupRefractoryischemiaNewMIHemodynamicinstabilityCrossoverfromEarlytoDelayed:11.9%CrossoverfromDelayedtoEarly:25%InterventionsandTimingEarlyN=1,593DelayedN=1,438CoronaryAngiography(%)97.695.5Mediantime(h±iqr)14(3-21)50(41-81)PCI(%)59.655.0Mediantime(h±iqr)16(3-23)52(41-101)CABG(%)14.713.6Mediantime(d±iqr)7.7(4.7-17.4)10.8(6.7-19.8)Iqr=interquartilerangeBaselineCharacteristicsEarlyN=1,593DelayedN=1,438Age65.165.8%Female34.834.7Diabetes26.527.3PriorMI19.720.9PriorPCI13.814.1PriorCABG7.07.3PriorStroke7.27.5IschemicECGΔ80.579.9ElevatedBiomarker77.276.9In-HospitalMedicationsEarlyN=1,593DelayedN=1,438ASA98.098.1Thieonopyridine87.286.7ThienopyridineorGPIIb/IIIainhibitor88.288.4GPIIb/IIIaInhibitor23.222.5AnticoagulantUFH24.624.6LMWH64.064.6Fondaparinux41.941.3Bivalirudin0.50.4BetaBlocker86.886.9Statin85.084.3PrimaryandSecondaryOutcomesEarlyN=1,593DelayedN=1,438HR95%CIPDeath,MI,Stroke9.711.40.850.68-1.060.15Death,MI,refractoryischemia9.613.10.720.58-0.890.002Death,MI,Stroke,refractoryischemia+repeatintervention16.719.70.840.71-0.990.039Death4.96.00.810.60-1.110.19MI30.61-1.140.25Stroke00.48-1.680.74Ref.Ischemia1.03.30.300.17-0.53<0.00001Rep.Intervention*40.82-1.340.73*At30days:5.9vs4.2%,HR1.39,95%CI1.00-1.95,P=0.047PrimaryOutcome

Death,MI,orStrokeDaysCumulativeHazard0.00.020.060.100306090120150180Death/MI/Strokeat180daysEarlyNo.atRiskDelayedEarly14381328126912541234122912111593148414131398139113821363DelayedHR0.8595%CI0.68-1.06P=0.15SecondaryOutcome

Death,MI,orrefractoryischemiaDaysCumulativeHazard0.00.040.080.120306090120150180Death/MI/RIat180daysDelayedEarlyNo.atRiskDelayedEarly14381303124312301209120511871593148514171402139413861366HR0.7295%CI0.58-0.79P=0.002SecondaryOutcome

Death,MI,stroke,RFIorRepInterventionDeath/MI/RI/Stroke/RepIntat180daysDaysCumulativeHazard0.00.000306090120150180DelayedEarlyNo.atRiskDelayedEarly14381250116611501128111810971593140013211304128712761256HR0.8495%CI0.71-0.99P=0.039SafetyOutcomesEarlyN=1,593DelayedN=1,438HRCIPMajorBleedduringinitialhospitalization80.60-1.310.53ICH00.1SurgIntervention0.40.8Retroperitoneal0.10.2↓Hb>=3g/dL2.32.6Transfusion≥2U2.22.9Pre-specifiedSubgroupsOverallAge<65>=65FemaleMaleNoSTdeviationSTdeviationNoelevatedmarkerElevatedMarkerGRACE0-140GRACE>=1413031129317361052197615231508668236320709619.76.57.611.714.10.4630.5400.7220.4230.00970.85(0.68-1.06)0.98(0.64-1.52)0.83(0.64-1.07)0.77(0.54-1.12)0.89(0.68-1.18)0.88(0.62-1.26)0.81(0.61-1.07)1.00(0.62-1.60)0.81(0.63-1.04)1.14(0.82-1.58)0.65(0.48-0.88)NCharacteristicHR(95%CI)Interactionp-Value0.301.52.03.0EarlybetterDelayedbetterHazardRatio(95%CI)Early%11.4

6.514.812.310.98.714.310.511.76.721.6Delayed%

GRACERiskScore:PrimaryOutcomeHR1.1495%CI0.82-1.58P=0.43HR0.6595%CI0.48-0.88P=0.005InteractionP=0.0097Low/IntRiskGRACEScore<140N=2070HighRiskGRACEScore>=140N=961Death,MIorStrokeat6mo.ConclusionsOverall,wefoundnosignificantdifferencebetweenanearlyandadelayedinvasivestrategyforpreventionofdeath,MIorstroke(primaryoutcome).However,inthesubgroupathighestrisk(GRACEscore>140),anearlyinvasivestrategywassuperiortoadelayedinvasivestrategyforpreventionofdeath,MIorstrokeTheearlyinvasivestrategyalsohadalargeimpactonreducingtherateofrefractoryischemiaby70%.TherewerenosignificantdifferencesinmajorbleedingorothersafetyconcernsbetweenthetwostrategiesImplicationsMostpatientswithACScanbemanagedsafelywitheitheranearlyoradelayedinvasivestrategyInasubsetofpatientsathighestrisk(GRACEscore>140),earlyinterventionissuperiorandthesepatientsshouldbetakentothecathlabasearlyaspossibleInallotherpatients,thedecisionregardingtimingofinterventioncandependonotherfactors,suchascathlabavailabilityandeconomicconsiderations.

TIMACS

AnInternationalRandomizedTrialofEarlyVersusDelayedInvasiveStrategiesinPatientswithNon-STSegmentElevationAcuteCoronarySyndromes

對(duì)比非ST段抬高的急性冠狀動(dòng)脈綜合征患者早期與延遲干預(yù)治療的國際隨機(jī)研究—中國亞組

TIMACS

AnInternationalRandomizedTrialofEarlyVersusDelayedInvasiveStrategiesinPatientswithNon-STSegmentElevationAcuteCoronarySyndromes共有815名患者入選本研究

早期介入組

446名，隨訪率98.4%

延遲介入組

369名，隨訪率98.8%臨床基線、合并用藥及冠造結(jié)果兩組無統(tǒng)計(jì)學(xué)差異

冠造的平均時(shí)間

早期介入組18.4小時(shí)

延遲介入組72.6小時(shí)

TIMACS

AnInternationalRandomizedTrialofEarlyVersusDelayedInvasiveStrategiesinPatientswithNon-STSegmentElevationAcuteCoronarySyndromes180天隨訪主要終點(diǎn)事件（死亡、心梗、卒中）

早期介入組

9.0%

延遲介入組

14.6%（P=0.01）

-死亡早期介入組3.6%

延遲介入組3.3%（P=0.79）

-心梗早期介入組5.2%

延遲介入組

10.8%（P=0.002）

-卒中早期介入組

0.2%

延遲介入組

0.5%（P=0.87）

TIMACS

AnInternationalRandomizedTrialofEarlyVersusDelayedInvasiveStrategiesinPatientswithNon-STSegmentElevationAcuteCoronarySyndromes180天隨訪次要終點(diǎn)事件死亡、心梗、難治性心肌缺血

早期介入組

14.6%

延遲介入組

22.0%（P=0.01）

死亡、心梗、卒中、難治性心肌缺血、再次血運(yùn)重建

早期介入組

26.7%

延遲介入組

30.4%（P=0.25）

TIMACS

AnInternationalRandomizedTrialofEarlyVersusDelayedInvasiveStrategiesinPatientswithNon-STSegmentElevationAcuteCoronarySyndromes***P≤0.05

TIMACS

AnInternationalRandomizedTrialofEarlyVersusDelayedInvasiveStrategiesinPatientswithNon-STSegmentElevationAcuteCoronarySyndromes30天隨訪主要終點(diǎn)事件（死亡、心梗、卒中）

早期介入組

8.1%

延遲介入組

12.5%（P=0.04）

-死亡早期介入組

2.9%

延遲介入組

2.2%（