ACS治療原則的學(xué)習(xí)教案

ACS治療原則的學(xué)習(xí)教案第1頁(yè)/共52頁(yè)EarlyRepolarizationBrugadaSyndromeAnteriorAMIPrinzmetalAnginaPericarditisAcuteInf.AMISTSegmentElevation(Transmuralischemia)Non-infarctSTElevation第2頁(yè)/共52頁(yè)STSegmentDepression(Non-transmuralischemia)STDepressionNSTEMITwaveinversionNSTEMI第3頁(yè)/共52頁(yè)第4頁(yè)/共52頁(yè)NSTEACS:KeyThemesNSTEACS:ahighriskpopulationpatientriskbenefitfromtreatmentwithmedications,aninvasivestrategyInteractionbetweeninvasivestrategyandpharmacologictxAntithromboticscornerstoneoftreatmentAnticoagulants:heparin,LMWH,directthrombininhibitorsAntiplateletagents:aspirin,IIb/IIIa,ADPinhibitors第5頁(yè)/共52頁(yè)AntmanEMetalNEnglJMed1996;335:1342-9第6頁(yè)/共52頁(yè)Invasivevs.ConservativeStrategyforACS

Deathor(re)-MI

TrialNPCIConsRITA318107.68.3VINO1316.322.4TACTICS22207.39.5TRUCS1487.616.7FRISCII245110.414.1MATE2019.96.7VANQUISH92024.012.2Overall7876Fox,Lancet360:743‘03Death/(re)Infarction

RR=0.88,p=0.05Interventionbetter

0.10.20.30.50.71.01.52.0Death/(re)-MI第7頁(yè)/共52頁(yè)CP971744-45

%ConsInvTACTICS–TIMI18TnTcutpoint=0.01ng/mL(54%ofptTnT+)TroponinT:Death,MI,RehospACS,6MonthsOR=0.52*P<0.001InteractionP<0.001P=NS*n=414n=396n=463n=495第8頁(yè)/共52頁(yè)BenefitsofanInvasiveStrategyinNon-STElevationACS

OnlyshowntoreducedeathandMIin highriskptsReducesre-hospitalization,anginain manyothersShortenshospitalization,maybecost effectiveWhatabouttheoptimaltimingofan invasivestrategy?第9頁(yè)/共52頁(yè)MedicalTxfor72-170hrThen,cathlabn=207Cathlab6hrn=203ISAR-COOLCP1107655-4NeumannFJetalJAMA2004

67%hadtroponin,65%hadSTdepression

Aspirin 500mg,100mgbid

Clopidogrel 600mg,75mgbid

Tirofiban 10mg/kgbolus,0.10mg/kg/mininfusion

Heparin (PTT60-85seconds)Non-STAcuteCoronarySyndrometroponinorSTdepressionn=410第10頁(yè)/共52頁(yè)ISAR-COOL

PrimaryEndpointCP1107655-230-dayeventrate(%)

Death&MI

DeathNeumannFJetalJAMA2004P=0.04P=0.23P=0.12P=0.56

AnynonfatalMINonfatalQ-waveMIRR1.96(1.01-3.82)

Coolingoff(n=207)

Earlyintervention(n=203)第11頁(yè)/共52頁(yè)TimingofanInvasiveStrategyinNon-STElevationACS

ISAR-REACTwasasmall,single centerstudy.Clinicaltrialsarestillgoing on.Otheranalysesalsoindicatethatcath within24hoursisbetterthanlatercathOughttouseintensiveantiplatelet therapywithaveryearlyinvasivestrategyWhatmedicaltherapyoughttobeusedinACS?第12頁(yè)/共52頁(yè)AntithromboticTrialists’Collaboration.BMJ.2002;324:71–86.

OR*0.51.01.52.0500–1500mg 34 19160–325mg 19 2675–150mg 12 32<75mg 3 13Anyaspirin 65 23AntiplateletBetterAntiplateletWorse

AspirinDose No.ofTrials (%)OddsRatio0AspirinDoseandEventsinHigh-RiskPts

FrequencyofCVDeath,MI,StrokeP=0.0001第13頁(yè)/共52頁(yè)CURECP999547-2YusufSetalNEJM2001;16:494-502Non-STelevationACS12,562patientsASA75to325mgpoqdplacebon=6,3033-12monthfollow-up(average9mo)ASA+clopidogrel(300mgload,75mgqd)n=6,259第14頁(yè)/共52頁(yè)CURE

CVDeath/MI/Stroke,1YearCP999731-3CVdeath,MI,stroke(%)Clopidogrel(n=6,303)Placebo(n=6,259)P=0.00003Daysafterenrollment第15頁(yè)/共52頁(yè)CUREEvent

rate

(%)RR0.80P=0.00005CP995058-6CVdeath,

MI,strokeClopidogrel(n=6,259)Placebo(n=6,303)AspirinandCV

deathMIStrokeNon-CV

deathRR0.92P=NSRR0.77P<0.001RR0.85P=NSRR0.96P=NS第16頁(yè)/共52頁(yè)CURE

Major/Life-ThreateningBleedsinthe7DaysAfterCABGPlaceboClopRRpStopped<5dayspriortoCABG:N=476N=436PtswithMajororLifeThreateningBleeding6.3%9.6%1.530.06MajorBleeds:

Significantlydisabling,intraocular,ortransfusion2unitsLifeThreatening:Hgb>5g/dl,hypotension(inotropes),surgerytostopbleeding,symptomaticICHortransfusion4units第17頁(yè)/共52頁(yè)ACC/AHAACSGuidelineUpdateClassIAspirin75to325mg/day(levelofevidence:A)ASAandclopidogrelfor9monthsafterNSTEACS(levelofevidence:B)Class3Donotadministerclopidogrelinthe5daysbeforeCABG BraunwaldE,etal.第18頁(yè)/共52頁(yè)Heparin(UForLMW)inACSWithoutST

DeathorMI

UFHorLMWH

Control

OR 95%CITheroux 2/122(1.6%) 4/121(3.3%) 0.50 0.10-2.53Cohen 0/37 1/32(3.1%) 0.12 0.01-5.89RISC 3/210(1.4%) 7/189(3.7%) 0.40 0.11-1.39Cohen 4/105(3.8%) 9/109(8.2%) 0.46 0.15-1.41Holdright* 42/154(27.3%) 40/131(30.5%) 0.85 0.51-1.43Gurfinkel 4/70(5.7%) 7/73(9.6%) 0.58 0.17-1.98

(UFH)Gurfinkel 0/68 7/73(9.6%) 0.13 0.03-0.60

(LMWH)FRISC 4/70(5.7%) 36/757(4.8%) 0.39 0.22-0.68UFHvs 55/698(7.9%) 68/655(10.4%) 0.67 0.45-0.99

placebo/controlLMWHvs 13/809(1.6%) 43/830(5.2%) 0.34 0.20-0.58

placeboTotal

68/1507(4.5%) 104/1412(7.4%) 0.53 0.38-0.73OnlyRCTs,placebooruntreatedcontrols

EikelboomJWetal:Lancet55:1936-42,2000CP951342-10.1Heparinbetter1.010.0Controlbetter第19頁(yè)/共52頁(yè)Trial: FRIC(dalteparin;n=1482)FRAXIS(nadroparin;n=2357)ESSENCE(enoxaparin;n=3171)

TIMIIIB(enoxaparin;n=3910)

.75 1.0 1.5(P=0.032)(P=0.029)BraunwaldEetal.Circulation2000;102:1193-1209LMWHBetterUFHBetterLMWHversusUFHinUA/NSTEMIManagedNon-invasively:

EffectonDeath,MI,RecurrentIschemia第20頁(yè)/共52頁(yè)CLASSIa（Ia級(jí)推薦）一旦出現(xiàn)UA/NSTEMI，需盡快在抗血小板治療的基礎(chǔ)上給予患者抗凝藥物。a.介入方案：證據(jù)級(jí)別A-包括依諾肝素和普通肝素；證據(jù)級(jí)別B-包括比伐盧定和戊聚糖鈉b.保守方案：藥物選擇可以是依諾肝素、普通肝素（證據(jù)級(jí)別A）或者戊聚糖鈉（證據(jù)級(jí)別B），有效性已經(jīng)確立。c.對(duì)于選擇保守治療的病人，如果有較高的出血風(fēng)險(xiǎn)，傾向于選擇戊聚糖鈉（證據(jù)級(jí)別B）CLASSIIa（IIa級(jí)推薦）對(duì)于最初選擇保守治療策略的UA/NSTEMI病人，作為抗凝治療，依諾肝素或者戊聚糖鈉要優(yōu)于普通肝素，除非計(jì)劃在24小時(shí)內(nèi)進(jìn)行冠脈搭橋手術(shù)。（證據(jù)級(jí)別B）2007年ACC/AHAUA/NSTEMI的指南抗凝治療推薦第21頁(yè)/共52頁(yè)ACC/AHA2007更新的抗凝治療指南高?；虼_診ACS實(shí)行導(dǎo)管或PCI疑似/確診ACS可能ACS阿司匹林+IVUFH/LMWH*GPIIb/IIIa拮抗劑阿司匹林+皮下LMWH*或IVUFH氯吡格雷氯吡格雷阿司匹林*證據(jù)等級(jí)Ia：依諾肝素優(yōu)于IVUFH第22頁(yè)/共52頁(yè)ACC/AHA治療建議2007“不穩(wěn)定型心絞痛/非ST段抬高心?；颊?，除非計(jì)劃在24小時(shí)內(nèi)行冠脈搭橋手術(shù)，相對(duì)于普通肝素，依諾肝素（Enoxaparin）作為抗凝劑應(yīng)優(yōu)先選用。(證據(jù)級(jí)別A)”2002updateACC/AHAguideline第23頁(yè)/共52頁(yè)ACCP7指南對(duì)LMWH的治療建議急性期LMWH優(yōu)于UFH（1B級(jí)）；LMWH治療時(shí)不需常規(guī)監(jiān)測(cè)（1C級(jí)）；已使用LMWH的患者如需進(jìn)行PCI，應(yīng)繼續(xù)使用LMWH（2C級(jí)）；應(yīng)用GPIIb/IIIa受體拮抗劑者，

LMWH安全性優(yōu)于UFH（2B級(jí)）。NSTEACS患者中LMWH的療程評(píng)價(jià)是：NSTEACS患者應(yīng)早期介入治療，如果冠脈干預(yù)延遲，可考慮延長(zhǎng)LMWH治療作為血運(yùn)重建的“橋梁”。第24頁(yè)/共52頁(yè)Restpain>5minandSTΔ

>0.1mVorDocumentedCADorCK-MBN=132Heparin70U/kgbolus+15U/kg/hrinfusion

Bivalirudin0.1mg/kgbolus+0.25mg/kginfusionTIMI-8:Bivalirudinvs.PlaceboinACS第25頁(yè)/共52頁(yè)TIMI-8:Bivalirudinvs.PlaceboinACS4-6wks7days4-6wks7daysp=0.008p=0.024p=NSp=NS第26頁(yè)/共52頁(yè)第27頁(yè)/共52頁(yè)BetaBlockersReduceCVdeath,MI,strokeby25-30%inhighriskptsNotwellstudiedinnon-STEACSReduceheartrate,bloodpressure,ischemia,chestdiscomfortClass1indication;qualityindicatorUseineveryonewithoutcontraindications第28頁(yè)/共52頁(yè)15.75.617.911.712.814.23.812.910.311.805101520PrimaryEndpoint%PlaceboGPIIb/IIIaPURSUIT

30daysPRISM

48hrsPRISM

PLUS

7daysP=0.04P=0.01P=0.004PARAGONA

30daysP=0.48PARAGONB

30daysP=0.33PlateletGPIIb/IIIaInhibitionforNon-STACS

PrimaryEndpointResultsfromthe5MajorRCTs第29頁(yè)/共52頁(yè)1.02.00.25AllPCItrials 17,393 0.66 8.5 5.6AllACStrials 24,311 0.89 12.8 11.4ACStroponin(+) 1,368 0.42 16.3 6.9ACSPCI 2,311 0.66 14.4 9.6ACSnoPCI 12,685 0.93 14.3 13.3ACStroponin(–) 2,901 1.05 6.2 6.5IIb/IIIaMeta-Analysis

30-DayDeath,MIat30DaysCP944328-1

Relative

risk Placebo IIb/IIIa

No. ratio (%) (%)ChewDPetal:JACC2000;36:2028–35IIb/IIIabetterPlacebobetter第30頁(yè)/共52頁(yè)IIb/IIIaInhibitorsinACSPatientsGreatestbenefitisduringPCIIfpursuinganon-invasivestrategy,recommendtreatingptswithelevatedtroponins,highTIMIscores,etc;probablythosewithdiabetes,markedSTsegmentshiftsDonotrecommendtheirroutineadministrationtoallACSptsinwhomanon-invasivestrategyisplanned第31頁(yè)/共52頁(yè)ConclusionsMuchremainstobelearnedabouttheoptimalmedicaltherapyforACSptsThedatafavoraninvasivestrategy,andsuggestdifferentmedicationsanddosesoughtbeadministeredifpursuinganinvasivevs.non-invasivestrategy,andinhighvs.lowriskpts第32頁(yè)/共52頁(yè)UA/NSTEMI:

PharmacologicalandMechanicalInterventionBraunwaldEetal.JAmCollCardiol2000;36:970-1062BraunwaldEetal.Circulation2002;106:1893-1900危險(xiǎn)分層(TIMI危險(xiǎn)評(píng)分)高危

TIMI評(píng)分5-7低危

TIMI評(píng)分0-2中危

TIMI評(píng)分3-4ASA+LMWH(普通肝素)+氯吡格雷依替巴肽/替羅非班ASA+LMWHor普通肝素+氯吡格雷ASA+LMWH(普通肝素)+氯吡格雷依替巴肽/替羅非班Cath/PCI/CABG進(jìn)行監(jiān)測(cè)/危險(xiǎn)評(píng)估缺血二級(jí)預(yù)防無(wú)缺血

第33頁(yè)/共52頁(yè)AlgorithmforPatientswithUA/NSTEMIManagedbyanInitialInvasiveStrategyProceedtoDiagnosticAngiographyASA(ClassI,LOE:A)ClopidogrelifASAintolerant(ClassI,LOE:A)DiagnosisofUA/NSTEMIisLikelyorDefiniteInvasiveStrategyInitiateA/CRx(ClassI,LOE:A)Acceptableoptions:enoxaparin

orUFH(ClassI,LOE:A)bivalirudinorfondaparinux(ClassI,LOE:B)SelectManagementStrategyProceedwithanInitialConservativeStrategyAndersonJL.JAmCollCardiol.2007,Inpress.Figure7ABB1B2PriortoAngiographyInitiateatleastone(ClassI,LOE:A)orboth(ClassIIa,LOE:B)ofthefollowing:ClopidogrelIVGPIIb/IIIainhibitorFactorsfavoringadminofbothclopidogrelandGPIIb/IIIainhibitorinclude:DelaytoAngiographyHighRiskFeaturesEarlyrecurrentischemicdiscomfort第34頁(yè)/共52頁(yè)Initiateclopidogrel(ClassI,LOE:A)ConsideraddingIVeptifibatideortirofiban(ClassIIb,LOE:B)ConservativeStrategyInitiateA/CRx(ClassI,LOE:A):

Acceptableoptions:enoxaparinorUFH(ClassI,LOE:A)orfondaparinux(ClassI,LOE:B),butenoxaparinorfondaparinuxarepreferable(ClassIIA,LOE:B)SelectManagementStrategyASA(ClassI,LOE:A)ClopidogrelifASAintolerant(ClassI,LOE:A)DiagnosisofUA/NSTEMIisLikelyorDefiniteAlgorithmforPatientswithUA/NSTEMIManagedbyanInitialConservativeStrategyProceedwithInvasiveStrategy(Continued)AndersonJL.JAmCollCardiol.2007.Inpress.Figure8

C2

C1

A第35頁(yè)/共52頁(yè)

EvidenceforPrimaryPCIasTreatmentofChoiceforSTEMIACS第36頁(yè)/共52頁(yè)

Summaryof23RandomizedTrials(n=7739)p=0.0003p<0.0001p=0.0004p<0.0001OR=0.57Keeley&GrinesLancet2003PCILyticRiskReductionDeath 28%Death/MI/CVA 43% PrimaryPCI:

ThePreferredReperfusionStrategy第37頁(yè)/共52頁(yè)P(yáng)rimary,Transfer,Facilitated&RescuePCIforSTEMI

PrimaryPCI

(PPCI) DirecttoCVLforPCIreperfusiontherapyTransferPCI PtstransferredfromhospitalswithoutPCIfacilities(no

lysis)toaPCIcentreFacilitatedPCI Patientsreceivingthrombolysis*followedbyintentionalPCIRescuePCI PCIafterfailedthrombolysis(at90mins)*ThrombolysismaybePre-hospital第38頁(yè)/共52頁(yè)第39頁(yè)/共52頁(yè)第40頁(yè)/共52頁(yè)Door-To-Balloon(DTB)Time

&ChoiceofReperfusionTherapyinSTEMI

Sxonset<3hr: FibrinolysisonlyifestimatedDTB>60minSxonset>3hrs<12hr: PrimaryPCIwithDTBof90min;otherwiseFibrinolysisisacceptablealternativeSxonset>12hr: NolysisbutPCImaystillbebeneficial第41頁(yè)/共52頁(yè)EvidenceforPre-HospitalThrombolysis forEarly(<2Hour)STEMI第42頁(yè)/共52頁(yè)EvidencetosupportTransfertoPCICentersfro