2015ESC非ST段抬高心肌梗死治疗指南

2015ESC非ST段抬高心肌梗死治疗指南

European Heart Journal Advance Access published August 29, 2015

EuropeanHeartJournal

ESCGUIDELINES

doi:10.1093/eurheartj/ehv320

2015ESCguidelinesforthemanagementofacutecoronarysyndromesinpatientspresentingwithoutpersistentST-segmentelevation

TaskForcefortheManagementofAcuteCoronarySyndromesinPatientsPresentingwithoutPersistentST-SegmentElevationoftheEuropeanSocietyofCardiology(ESC)

Authors/TaskForceMembers:MarcoRof *(Chairperson)(Switzerland),CarloPatrono*(Co-Chairperson)(Italy),Jean-PhilippeCollet (France),ChristianMueller (Switzerland),MarcoValgimigli (TheNetherlands),FelicitaAndreotti(Italy),

JeroenJ.Bax(TheNetherlands),MichaelA.Borger(Germany),CarlosBrotons(Spain),DerekP.Chew(Australia),BarisGencer(Switzerland),GerdHasenfuss(Germany),KeldKjeldsen(Denmark),PatrizioLancellotti(Belgium),UlfLandmesser(Germany),JulindaMehilli(Germany),DebabrataMukherjee(USA),RobertF.Storey(UK),andStephanWindecker(Switzerland)

DocumentReviewers:HelmutBaumgartner(CPGReviewCoordinator)(Germany),OliverGaemperli(CPGReviewCoordinator)(Switzerland),StephanAchenbach(Germany),StefanAgewall(Norway),LinaBadimon(Spain),

ColinBaigent(UK),He

´ctorBueno(Spain),RaffaeleBugiardini(Italy),ScipioneCarerj(Italy),FilipCasselman(Belgium),ThomasCuisset(France),ÇetinErol(Turkey),DonnaFitzsimons(UK),MartinHalle

(Germany),

*Correspondingauthors:MarcoRof ,DivisionofCardiology,UniversityHospital,RueGabriellePerret-Gentil4,1211Geneva14,Switzerland,Tel:+41223723743,Fax:+41223727229,E-mail:Marco.Rof @hcuge.ch

CarloPatrono,IstitutodiFarmacologia,Universita

`CattolicadelSacroCuore,LargoF.Vito1,IT-00168Rome,Italy,Tel:+390630154253,Fax:+39063050159,E-mail:carlo.patrono@rm.unicatt.it

SectionCoordinatorsaf liationslistedintheAppendix.

ESCCommitteeforPracticeGuidelines(CPG)andNationalCardiacSocietiesdocumentreviewerslistedintheAppendix.ESCentitieshavingparticipatedinthedevelopmentofthisdocument:

Associations:AcuteCardiovascularCareAssociation(ACCA),EuropeanAssociationforCardiovascularPrevention&Rehabilitation(EACPR),EuropeanAssociationofCardiovas-cularImaging(EACVI),EuropeanAssociationofPercutaneousCardiovascularInterventions(EAPCI),HeartFailureAssociation(HFA).

Councils:CouncilonCardiovascularNursingandAlliedProfessions(CCNAP),CouncilforCardiologyPractice(CCP),CouncilonCardiovascularPrimaryCare(CCPC).WorkingGroups:WorkingGrouponCardiovascularPharmacotherapy,WorkingGrouponCardiovascularSurgery,WorkingGrouponCoronaryPathophysiologyandMicrocir-culation,WorkingGrouponThrombosis.

ThecontentoftheseEuropeanSocietyofCardiology(ESC)Guidelineshasbeenpublishedforpersonalandeducationaluseonly.Nocommercialuseisauthorized.NopartoftheESCGuidelinesmaybetranslatedorreproducedinanyformwithoutwrittenpermissionfromtheESC.PermissioncanbeobtaineduponsubmissionofawrittenrequesttoOxfordUniversityPress,thepublisheroftheEuropeanHeartJournalandthepartyauthorizedtohandlesuchpermissionsonbehalfoftheESC.

Disclaimer:TheESCGuidelinesrepresenttheviewsoftheESCandwereproducedaftercarefulconsiderationofthescienti candmedicalknowledgeandtheevidenceavailableatthetimeoftheirpublication.TheESCisnotresponsibleintheeventofanycontradiction,discrepancyand/orambiguitybetweentheESCGuidelinesandanyotherof cialrecom-mendationsorguidelinesissuedbytherelevantpublichealthauthorities,inparticularinrelationtogooduseofhealthcareortherapeuticstrategies.Healthprofessionalsareencour-agedtotaketheESCGuidelinesfullyintoaccountwhenexercisingtheirclinicaljudgment,aswellasinthedeterminationandtheimplementationofpreventive,diagnosticortherapeuticmedicalstrategies;however,theESCGuidelinesdonotoverride,inanywaywhatsoever,theindividualresponsibilityofhealthprofessionalstomakeappropriateandaccuratedecisionsinconsiderationofeachpatient’shealthconditionandinconsultationwiththatpatientand,whereappropriateand/ornecessary,thepatient’scaregiver.NordotheESCGuidelinesexempthealthprofessionalsfromtakingintofullandcarefulconsiderationtherelevantof cialupdatedrecommendationsorguidelinesissuedbythecompetentpublichealthauthorities,inordertomanageeachpatient’scaseinlightofthescienti callyaccepteddatapursuanttotheirrespectiveethicalandprofessionalobligations.Itisalsothehealthprofessional’sresponsibilitytoverifytheapplicablerulesandregulationsrelatingtodrugsandmedicaldevicesatthetimeofprescription.

&TheEuropeanSocietyofCardiology2015.Allrightsreserved.Forpermissionspleaseemail:journals.permissions@http://www.77cn.com.cn.

Downloaded from http://www.77cn.com.cn/ by guest on August 30, 2015

2015ESC非ST段抬高心肌梗死治疗指南

Page2of59

ESCGuidelines

ChristianHamm(Germany),DavidHildick-Smith(UK),KurtHuber(Austria),EfstathiosIliodromitis(Greece),StefanJames(Sweden),BasilS.Lewis(Israel),GregoryY.H.Lip(UK),MassimoF.Piepoli(Italy),DimitriosRichter(Greece),ThomasRosemann(Switzerland),UdoSechtem(Germany),Ph.GabrielSteg(France),ChristianVrints(Belgium),andJoseLuisZamorano(Spain)

Thehttp://www.77cn.com.cn/guidelines

disclosureformsofallexpertsinvolvedinthedevelopmentoftheseguidelinesareavailableontheESCwebsite-Keywords

-------------------------Acute--------cardiac--------care------ ---Acute-------coronary-----------syndromes-------------- ---Angioplasty-------------- ---Anticoagulation------------------- ---Apixaban----------- ---Aspirin--------- --Atherothrombosis Beta-blockers Bivalirudin Bypasssurgery Cangrelor Chestpainunit Clopidogrel Dabigatran Diabetes Earlyinvasivestrategy Enoxaparin EuropeanSocietyofCardiology Fondaparinux GlycoproteinIIb/IIIainhibitors Guidelines Heparin High-sensitivitytroponin Myocardialischaemia Nitrates Non-ST-elevationmyocardialinfarction Plateletinhibition Prasugrel Recommendations Revascularization Rhythmmonitoring Rivaroxaban Statin Stent Ticagrelor Unstableangina Vorapaxar

TableofContents

Abbreviationsandacronyms........................45.1.1Generalsupportivemeasures...............151.Preamble...................................55.1.2Nitrates.............................152.Introduction.................................

75.1.3Beta-blockers..........................152.1De nitions,pathophysiologyandepidemiology.......75.1.4Otherdrugclasses(seeWebaddenda).........16

2.1.1Universalde nitionofmyocardialinfarction......75.1.5Recommendationsforanti-ischaemicdrugsin2.1.1.1Type1MI.........................7theacutephaseofnon-ST-elevationacutecoronary2.1.1.2Type2MI.........................7syndromes...............................162.1.2Unstableanginaintheeraofhigh-sensitivitycardiac5.2Plateletinhibition..........................16troponinassays............................75.2.1Aspirin..............................162.1.3Pathophysiologyandepidemiology

5.2.2P2Y12inhibitors........................16(seeWebaddenda).........................75.2.2.1Clopidogrel........................163.Diagnosis...................................

75.2.2.2Prasugrel..........................163.1Clinicalpresentation........................75.2.2.3Ticagrelor.........................173.2Physicalexamination........................85.2.2.4Cangrelor.........................183.3Diagnostictools...........................85.2.3TimingofP2Y12inhibitoradministration........193.3.1Electrocardiogram......................85.2.4MonitoringofP2Y12inhibitors

3.3.2Biomarkers...........................9(seeWebaddenda).........................193.3.3‘Rule-in’and‘rule-out’algorithms.............105.2.5Prematurediscontinuationoforalantiplatelet3.3.4Non-invasiveimaging.....................11therapy..................................193.3.4.1Functionalevaluation..................115.2.6Durationofdualantiplatelettherapy...........193.3.4.2Anatomicalevaluation.................115.2.7GlycoproteinIIb/IIIainhibitors...............203.4Differentialdiagnosis........................125.2.7.1Upstreamversusproceduralinitiation4.Riskassessmentandoutcomes.....................

12(seeWebaddenda)........................204.1Clinicalpresentation,electrocardiogramandbiomarkers125.2.7.2CombinationwithP2Y12inhibitors

4.1.1Clinicalpresentation.....................12(seeWebaddenda)........................204.1.2Electrocardiogram......................125.2.7.3Adjunctiveanticoagulanttherapy

4.1.3Biomarkers...........................13(seeWebaddenda)........................204.2Ischaemicriskassessment.....................135.2.8Vorapaxar(seeWebaddenda)..............204.2.1Acuteriskassessment....................135.2.9Recommendationsforplateletinhibitionin4.2.2Cardiacrhythmmonitoring.................13non-ST-elevationacutecoronarysyndromes.........204.2.3Long-termrisk.........................145.3Anticoagulation...........................214.3Bleedingriskassessment.....................14

5.3.1Anticoagulationduringtheacutephase.........214.4Recommendationsfordiagnosis,riskstrati cation,imaging5.3.1.1Unfractionatedheparin................21andrhythmmonitoringinpatientswithsuspectednon-ST-5.3.1.2Lowmolecularweightheparin............22elevationacutecoronarysyndromes................145.3.1.3Fondaparinux.......................225.Treatment..................................

155.3.1.4Bivalirudin.........................225.1Pharmacologicaltreatmentofischaemia...........

15

5.3.2Anticoagulationfollowingtheacutephase...

....

23

Downloaded from http://www.77cn.com.cn/ by guest on August 30, 2015

2015ESC非ST段抬高心肌梗死治疗指南

non-ST-elevationacutecoronarysyndromes.........235.4Managingoralantiplateletagentsinpatientsrequiringlong-termoralanticoagulants.....................245.4.1Patientsundergoingpercutaneouscoronary

intervention...............................245.4.2Patientsmedicallymanagedorrequiringcoronaryarterybypasssurgery........................26

5.4.3Recommendationsforcombiningantiplateletagentsandanticoagulantsinnon-ST-elevationacutecoronarysyndromepatientsrequiringchronicoralanticoagulation.265.5Managementofacutebleedingevents

(seeWebaddenda)...........................275.5.1Generalsupportivemeasures(seeWebaddenda)..275.5.2Bleedingeventsonantiplateletagents

(seeWebaddenda).........................275.5.3BleedingeventsonvitaminKantagonists

(seeWebaddenda).........................275.5.4Bleedingeventsonnon-vitaminKantagonistoralanticoagulants(seeWebaddenda)................275.5.5Non-access-relatedbleedingevents

(seeWebaddenda).........................275.5.6Bleedingeventsrelatedtopercutaneouscoronaryintervention(seeWebaddenda).................275.5.7Bleedingeventsrelatedtocoronaryarterybypasssurgery(seeWebaddenda)....................275.5.8Transfusiontherapy(seeWebaddenda)........27

5.5.9Recommendationsforbleedingmanagementandbloodtransfusioninnon-ST-elevationacutecoronary

syndromes...............................275.6Invasivecoronaryangiographyandrevascularization...285.6.1Invasivecoronaryangiography...............285.6.1.1Patternofcoronaryarterydisease.........285.6.1.2Identi cationoftheculpritlesion..........285.6.1.3Fractional owreserve.................295.6.2Routineinvasivevs.selectiveinvasiveapproach....295.6.3Timingofinvasivestrategy.................295.6.3.1Immediateinvasivestrategy(,2h).........295.6.3.2Earlyinvasivestrategy(,24h)...........295.6.3.3Invasivestrategy(,72h)...............305.6.3.4Selectiveinvasivestrategy...............305.6.4Conservativetreatment...................305.6.4.1Inpatientswithcoronaryarterydisease......305.6.4.1.1Non-obstructiveCAD..............305.6.4.1.2CADnotamenabletorevascularization...315.6.4.2Inpatientswithnormalcoronaryangiogram(seeWebaddenda)........................315.6.5Percutaneouscoronaryintervention...........315.6.5.1Technicalaspectsandchallenges..........315.6.5.2Vascularaccess......................315.6.5.3Revascularizationstrategiesandoutcomes....325.6.6Coronaryarterybypasssurgery..............325.6.6.1Timingofsurgeryandantithromboticdrug

discontinuation(seeWebaddenda).............32

5.6.6.2Recommendationsforperioperative

managementofantiplatelettherapyinnon-ST-elevation

arterybypasssurgery.......................325.6.6.3Technicalaspectsandoutcomes

(seeWebaddenda)........................335.6.7Percutaneouscoronaryinterventionvs.coronaryarterybypasssurgery........................335.6.8Managementofpatientswithcardiogenicshock...33

5.6.9Recommendationsforinvasivecoronaryangiographyandrevascularizationinnon-ST-elevationacutecoronarysyndromes...............................345.7Genderspeci cities(seeWebaddenda)...........345.8Specialpopulationsandconditions(seeWebaddenda).345.8.1Theelderlyandfrailpatients(seeWebaddenda)..34

5.8.1.1Recommendationsforthemanagementofelderlypatientswithnon-ST-elevationacutecoronarysyndromes..............................345.8.2Diabetesmellitus(seeWebaddenda)..........35

5.8.2.1Recommendationsforthemanagementof

diabeticpatientswithnon-ST-elevationacutecoronarysyndromes..............................355.8.3Chronickidneydisease(seeWebaddenda)......355.8.3.1Doseadjustmentofantithromboticagents

(seeWebaddenda)........................35

5.8.3.2Recommendationsforthemanagementofpatientswithchronickidneydiseaseandnon-ST-elevationacutecoronarysystems...............355.8.4Leftventriculardysfunctionandheartfailure(seeWebaddenda).............................36

5.8.4.1Recommendationsforthemanagementof

patientswithacuteheartfailureinthesettingofnon-ST-elevationacutecoronarysyndromes.............36

5.8.4.2Recommendationsforthemanagementofpatientswithheartfailurefollowingnon-ST-elevationacutecoronarysyndromes...................365.8.5Atrial brillation(seeWebaddenda)..........37

5.8.5.1Recommendationsforthemanagementofatrial brillationinpatientswithnon-ST-elevationacute

coronarysyndromes.......................375.8.6Anaemia(seeWebaddenda)...............375.8.7Thrombocytopenia(seeWebaddenda)........375.8.7.1ThrombocytopeniarelatedtoGPIIb/IIIa

inhibitors(Webaddenda)....................375.8.7.2Heparin-inducedthrombocytopenia(Web

addenda)...............................37

5.8.7.3Recommendationsforthemanagementofthrombocytopeniainnon-ST-elevationacutecoronarysyndromes..............................375.8.8Patientsrequiringchronicanalgesicoranti-in ammatorytreatment(seeWebaddenda).........375.8.9Non-cardiacsurgery(seeWebaddenda)........375.9Long-termmanagement......................385.9.1Medicaltherapyforsecondaryprevention.......385.9.1.1Lipid-loweringtreatment...............385.9.1.2Antithrombotictherapy................385.9.1.3ACEinhibition......................385.9.1.4Beta-blockers.......................

38

Downloaded from http://www.77cn.com.cn/ by guest on August 30, 2015

2015ESC非ST段抬高心肌梗死治疗指南

5.9.1.7Glucose-loweringtherapyindiabeticpatients..385.9.2Lifestylechangesandcardiacrehabilitation.......385.9.3Recommendationsforlong-termmanagementafternon-ST-elevationacutecoronarysyndromes.........386.Performancemeasures..........................397.Summaryofmanagementstrategy...................398.Gapsinevidence..............................419.Todoandnotdomessagesfromtheguidelines..........4110.Webaddendaandcompaniondocuments.............

4211.Acknowledgements.........................4212.Appendix..................................

4213.References..............................

43

Abbreviationsandacronyms

ACC

AmericanCollegeofCardiology

ACCOAST

ComparisonofPrasugrelattheTimeofPercutaneousCoronaryInterventionorasPretreatmentattheTimeofDiagnosisinPatientswithNon-STElevationMyocardialInfarction

ACEangiotensin-convertingenzymeACSacutecoronarysyndromesACTactivatedclottingtime

ACTIONAcuteCoronaryTreatmentandInterventionOutcomesNetwork

ACUITYAcuteCatheterizationandUrgentInterven-tionTriagestrategY

ADAPT-DESAssessmentofDualAntiPlateletTherapywithDrug-ElutingStentsADPadenosinediphosphate

AHA

AmericanHeartAssociation

APPRAISEApixabanforPreventionofAcuteIschaemicEvents

aPTTactivatedpartialthromboplastintimeARB

angiotensinreceptorblocker

ATLASACSAnti-XaTherapytoLowerCardiovascular2-TIMI51

EventsinAdditiontoAspirinWithorWith-outThienopyridineTherapyinSubjectswithAcuteCoronarySyndrome–ThrombolysisinMyocardialInfarction51ATPadenosinetriphosphate

BARCBleedingAcademicResearchConsortiumBMSbare-metalstent

CABGcoronaryarterybypassgraftCAD

coronaryarterydisease

CHA2DS2-VASc

Cardiacfailure,Hypertension,Age≥75(2points),Diabetes,Stroke(2points)–Vasculardisease,Age65–74,SexcategoryCHAMPION

CangrelorversusStandardTherapytoAchieveOptimalManagementofPlateletInhibition

CIcon denceintervalCK

creatinekinase

COXcyclooxygenase

CMRcardiacmagneticresonance

CPGCommitteeforPracticeGuidelines

CREDO

ClopidogrelfortheReductionofEventsDuringObservation

CRUSADECanRapidriskstrati cationofUnstablean-ginapatientsSuppressADverseoutcomes

withEarlyimplementationoftheACC/AHAguidelines

CTcomputedtomographyCUREClopidogrelinUnstableAnginatoPrevent

RecurrentEvents

CURRENT-OASISClopidogrelandAspirinOptimalDoseUsage7toReduceRecurrentEvents–SeventhOrgan-izationtoAssessStrategiesinIschaemic

Syndromes

CVcardiovascularCYPcytochromeP450DAPTdual(oral)antiplatelettherapyDESdrug-elutingstentEARLY-ACSEarlyGlycoproteinIIb/IIIaInhibitionin

Non-ST-SegmentElevationAcuteCoronarySyndrome

ECGelectrocardiogrameGFRestimatedglomerular ltrationrateEMAEuropeanMedicinesAgencyESCEuropeanSocietyofCardiologyFDAFoodandDrugAdministrationFFRfractional owreserveFREEDOMFutureRevascularizationEvaluationin

PatientswithDiabetesMellitus:OptimalManagementofMultivesselDisease

GPIIb/IIIaglycoproteinIIb/IIIaGRACE2.0GlobalRegistryofAcuteCoronaryEvents2.0GUSTOGlobalUtilizationofStreptokinaseandTPA

forOccludedArteries

GWTGGetWithTheGuidelinesHAS-BLEDhypertension,abnormalrenalandliverfunc-tion(1pointeach),stroke,bleedinghistory

orpredisposition,labileINR,elderly(.65years),drugsandalcohol(1pointeach)

HITheparin-inducedthrombocytopeniaHORIZONSHarmonizingOutcomeswithRevasculariza-tiONandStentsinAcuteMyocardialInfarctionHRhazardratioIABP-ShockIIIntra-AorticBalloonPumpinCardiogenic

ShockII

IMPROVE-ITIMProvedReductionofOutcomes:Vytorin

Ef cacyInternationalTrial

INRinternationalnormalizedratioISAR-CLOSUREInstrumentalSealingofARterialpuncture

site–CLOSUREdeviceversusmanualcompression

ISAR-REACTIntracoronarystentingandAntithrombotic

Regimen–RapidEarlyActionforCoronaryTreatment

Downloaded from http://www.77cn.com.cn/ by guest on August 30, 2015

2015ESC非ST段抬高心肌梗死治疗指南

ESCGuidelines

ISAR-TRIPLEi.v.LDLLMWHLVLVEFMACEMATRIX

MDCTMERLIN

MIMINAPNOACNSAIDNSTE-ACSNSTEMINYHAOACOASISOR

PARADIGM-HF

PCI

PEGASUS-TIMI54

PLATOPOISERCTRIVALRRRRR

SAFE-PCIs.c.STEMI

SWEDEHEART

SYNERGY

SYNTAXTACTICS

TripleTherapyinPatientsonOralAnticoagula-tionAfterDrugElutingStentImplantationintravenous

low-densitylipoprotein

lowmolecularweightheparinleftventricular

leftventricularejectionfractionmajoradversecardiovascularevent

MinimizingAdverseHaemorrhagicEventsbyTRansradialAccessSiteandSystemicImple-mentationofangioX

multidetectorcomputedtomography

MetabolicEf ciencyWithRanolazineforLessIschaemiainNon-ST-ElevationAcuteCoron-arySyndromes

myocardialinfarction

MyocardialInfarctionNationalAuditProjectnon-vitaminKantagonistoralanticoagulantnon-steroidalanti-in ammatorydrug

non-ST-elevationacutecoronarysyndromesnon-ST-elevationmyocardialinfarctionNewYorkHeartAssociationoralanticoagulation/anticoagulant

OrganizationtoAssessStrategiesforIschae-micSyndromesoddsratio

ProspectivecomparisonofARNIwithACEItoDetermineImpactonGlobalMortalityandmorbidityinHeartFailure

percutaneouscoronaryintervention

PreventionofCardiovascularEventsinPa-tientswithPriorHeartAttackUsingTicagre-lorComparedtoPlaceboonaBackgroundofAspirin-ThrombolysisinMyocardialInfarction54

PLATeletinhibitionandpatientOutcomesPeriOperativeISchemicEvaluationrandomizedcontrolledtrial

RadIalVsfemorALaccessforcoronaryinterventionrelativerisk

relativeriskreduction

StudyofAccessSiteforEnhancementofPCIforWomensubcutaneous

ST-segmentelevationmyocardialinfarctionSwedishWeb-systemforEnhancementandDevelopmentofEvidence-basedcareinHeartdiseaseEvaluatedAccordingtoRecom-mendedTherapies

SuperiorYieldoftheNewStrategyofEnoxa-parin,RevascularizationandGlycoproteinIIb/IIIaInhibitorstrial

SYNergybetweenpercutaneouscoronaryinterventionwithTAXusandcardiacsurgeryTreatanginawithAggrastatanddetermineCostofTherapywithanInvasiveorConser-vativeStrategy

Page5of59

TIAtransientischaemicattack

TIMACSTimingofInterventioninPatientswithAcuteCoronarySyndromes

TIMI

ThrombolysisInMyocardialInfarction

TRA2P-TIMI50

ThrombinReceptorAntagonistinSecondaryPreventionofAtherothromboticIschemicEvents–ThrombolysisinMyocardialInfarc-tion50

TRACER

ThrombinReceptorAntagonistforClinicalEventReductioninAcuteCoronarySyndrome

TRILOGYACS

TargetedPlateletInhibitiontoClarifytheOp-timalStrategytoMedicallyManageAcuteCoronarySyndromes

TRITON-TIMI38

TRialtoAssessImprovementinTherapeuticOutcomesbyOptimizingPlateletInhibitioNwithPrasugrel–ThrombolysisInMyocardialInfarction38

TVRtargetvesselrevascularizationUFHunfractionatedheparinVKAvitaminKantagonist

WOEST

WhatistheOptimalantiplatEletandanti-coagulanttherapyinpatientswithOACandcoronaryStenTing

ZEUS

Zotarolimus-elutingEndeavorSprintStentinUncertainDESCandidates

1.Preamble

Guidelinessummarizeandevaluateallavailableevidenceonapar-ticularissueatthetimeofthewritingprocess,withtheaimofassist-inghealthprofessionalsinselectingthebestmanagementstrategiesforanindividualpatientwithagivencondition,takingintoaccounttheimpactonoutcome,aswellastherisk–bene tratioofparticu-lardiagnosticortherapeuticmeans.Guidelinesandrecommenda-tionsshouldhelphealthprofessionalstomakedecisionsintheirdailypractice.However,the naldecisionsconcerninganindividualpatientmustbemadebytheresponsiblehealthprofessional(s)inconsultationwiththepatientandcaregiverasappropriate.

AgreatnumberofGuidelineshavebeenissuedinrecentyearsbytheEuropeanSocietyofCardiology(ESC)aswellasbyothersoci-etiesandorganisations.Becauseoftheimpactonclinicalpractice,qualitycriteriaforthedevelopmentofguidelineshavebeenestab-lishedinordertomakealldecisionstransparenttotheuser.There-commendationsforformulatingandissuingESCGuidelinescanbefoundontheESCwebsite(http://www.77cn.com.cn/Guidelines-&-Education/Clinical-Practice-Guidelines/Guidelines-development/Writing-ESC-Guidelines).ESCGuidelinesrepresenttheof cialpos-itionoftheESConagiventopicandareregularlyupdated.

MembersofthisTaskForcewereselectedbytheESCtore-presentprofessionalsinvolvedwiththemedicalcareofpatientswiththispathology.Selectedexpertsinthe eldundertookacom-prehensivereviewofthepublishedevidenceformanagement(includingdiagnosis,treatment,preventionandrehabilitation)ofagivenconditionaccordingtoESCCommitteeforPracticeGuide-lines(CPG)policy.Acriticalevaluationofdiagnosticandtherapeuticprocedureswasperformed,includingassessmentofthe

Downloaded from http://www.77cn.com.cn/ by guest on August 30, 2015

2015ESC非ST段抬高心肌梗死治疗指南

risk–bene tratio.Estimatesofexpectedhealthoutcomesforlargerpopulationswereincluded,wheredataexist.Thelevelofevidenceandthestrengthoftherecommendationofparticularmanagementoptionswereweighedandgradedaccordingtoprede nedscales,asoutlinedinTables1and2.

Theexpertsofthewritingandreviewingpanelsprovideddeclar-ationofinterestformsforallrelationshipsthatmightbeperceivedasrealorpotentialsourcesofcon ictsofinterest.Theseformswerecompiledintoone leandcanbefoundontheESCwebsite(http://www.77cn.com.cn/guidelines).Anychangesindeclarationsofinterestthatariseduringthewritingperiodmustbenoti edtotheESCandupdated.TheTaskForcereceiveditsentire nancialsupportfromtheESCwithoutanyinvolvementfromthehealthcareindustry.

TheESCCPGsupervisesandcoordinatesthepreparationofnewTheNationalSocietiesoftheESCareencouragedtoendorse,Guidelinesproducedbytaskforces,expertgroupsorconsensuspa-translateandimplementallESCGuidelines.Implementationpro-nels.TheCommitteeisalsoresponsiblefortheendorsementpro-grammesareneededbecauseithasbeenshownthattheoutcomecessoftheseGuidelines.TheESCGuidelinesundergoextensiveofdiseasemaybefavourablyin uencedbythethoroughapplica-reviewbytheCPGandexternalexperts.Afterappropriaterevi-tionofclinicalrecommendations.

sionstheGuidelinesareapprovedbyalltheexpertsinvolvedinSurveysandregistriesareneededtoverifythatreal-lifedailyprac-theTaskForce.The nalizeddocumentisapprovedbytheCPGticeisinkeepingwithwhatisrecommendedintheguidelines,thusforpublicationintheEuropeanHeartJournal.TheGuidelinescompletingtheloopbetweenclinicalresearch,writingofguidelines,weredevelopedaftercarefulconsiderationofthescienti cdisseminatingthemandimplementingthemintoclinicalpractice.andmedicalknowledgeandtheevidenceavailableatthetimeofHealthprofessionalsareencouragedtotaketheESCGuidelinestheirdating.

fullyintoaccountwhenexercisingtheirclinicaljudgment,aswellasThetaskofdevelopingESCGuidelinescoversnotonlyinthedeterminationandtheimplementationofpreventive,diagnos-integrationofthemostrecentresearch,butalsothecreationofticortherapeuticmedicalstrategies.However,theESCGuidelineseducationaltoolsandimplementationprogrammesfortherecom-donotoverrideinanywaywhatsoevertheindividualresponsibilitymendations.Toimplementtheguidelines,condensedpocketofhealthprofessionalstomakeappropriateandaccuratedecisionsguidelinesversions,summaryslides,bookletswithessentialmes-inconsiderationofeachpatient’shealthconditionandinconsult-sages,summarycardsfornon-specialistsandanelectronicversionationwiththatpatientandthepatient’scaregiverwhereappropriatefordigitalapplications(smartphones,etc.)areproduced.Theseand/ornecessary.Itisalsothehealthprofessional’sresponsibilitytoversionsareabridgedandthus,ifneeded,oneshouldalwaysreferverifytherulesandregulationsapplicabletodrugsanddevicesatthetothefulltextversionwhichisfreelyavailableontheESCwebsite.

timeofprescription.

Downloaded from http://www.77cn.com.cn/ by guest on August 30, 2015

2015ESC非ST段抬高心肌梗死治疗指南

ESCGuidelines

2.Introduction

2.1De nitions,pathophysiologyandepidemiology

Theleadingsymptomthatinitiatesthediagnosticandtherapeuticcascadeinpatientswithsuspectedacutecoronarysyndromes(ACS)ischestpain.Basedontheelectrocardiogram(ECG),twogroupsofpatientsshouldbedifferentiated:

(1)Patientswithacutechestpainandpersistent(.20min)

ST-segmentelevation.

ThisconditionistermedST-elevationACSandgenerallyre- ectsanacutetotalcoronaryocclusion.Mostpatientswillultim-atelydevelopanST-elevationmyocardialinfarction(STEMI).Themainstayoftreatmentinthesepatientsisimmediatereperfusionbyprimaryangioplastyor brinolytictherapy.1

(2)PatientswithacutechestpainbutnopersistentST-segment

elevation.

ECGchangesmayincludetransientST-segmentelevation,persistentortransientST-segmentdepression,T-waveinver-sion, atTwavesorpseudo-normalizationofTwavesortheECGmaybenormal.Theclinicalspectrumofnon-ST-elevationACS(NSTE-ACS)mayrangefrompatientsfreeofsymptomsatpresentationtoindividualswithongoingischaemia,electricalorhaemodynamicinstabilityorcardiacarrest.Thepathologicalcorrelateatthemyocardialleveliscardiomyocytenecrosis[NSTE-myocardialinfarction(NSTEMI)]or,lessfrequently,myocardialischaemiawithoutcellloss(unstableangina).Asmallproportionofpatientsmaypresentwithongoingmyocardialischaemia,characterizedbyoneormoreofthefollow-ing:recurrentorongoingchestpain,markedSTdepressionon12-leadECG,heartfailureandhaemodynamicorelectricalinstabil-ity.Duetotheamountofmyocardiuminjeopardyandtheriskofmalignantventriculararrhythmias,immediatecoronaryangiographyand,ifappropriate,revascularizationareindicated.

2.1.1Universalde nitionofmyocardialinfarction

Acutemyocardialinfarction(MI)de nescardiomyocytenecrosisinaclinicalsettingconsistentwithacutemyocardialischaemia.2AcombinationofcriteriaisrequiredtomeetthediagnosisofacuteMI,namelythedetectionofanincreaseand/ordecreaseofacardiacbiomarker,preferablyhigh-sensitivitycardiactroponin,withatleastonevalueabovethe99thpercentileoftheupperreferencelimitandatleastoneofthefollowing:

(1)Symptomsofischaemia.

(2)Neworpresumednewsigni cantST-Twavechangesorleft

bundlebranchblockon12-leadECG.

(3)DevelopmentofpathologicalQwavesonECG.

(4)Imagingevidenceofneworpresumednewlossofviablemyo-cardiumorregionalwallmotionabnormality.

(5)Intracoronarythrombusdetectedonangiographyorautopsy.2.1.1.1Type1MI

Type1MIischaracterizedbyatheroscleroticplaquerupture,ulcer-ation, ssure,erosionordissectionwithresultingintraluminalthrombusinoneormorecoronaryarteriesleadingtodecreased

Page7of59

myocardialblood owand/ordistalembolizationandsubsequentmyocardialnecrosis.Thepatientmayhaveunderlyingseverecoron-aryarterydisease(CAD)but,onoccasion(i.e.5–20%ofcases),theremaybenon-obstructivecoronaryatherosclerosisornoangio-graphicevidenceofCAD,particularlyinwomen.2–5

2.1.1.2Type2MI

Type2MIismyocardialnecrosisinwhichaconditionotherthancor-onaryplaqueinstabilitycontributestoanimbalancebetweenmyo-cardialoxygensupplyanddemand.2Mechanismsincludecoronaryarteryspasm,coronaryendothelialdysfunction,tachyarrhythmias,bradyarrhythmias,anaemia,respiratoryfailure,hypotensionandse-verehypertension.Inaddition,incriticallyillpatientsandinpatientsundergoingmajornon-cardiacsurgery,myocardialnecrosismayberelatedtoinjuriouseffectsofpharmacologicalagentsandtoxins.6

Theuniversalde nitionofMIalsoincludestype3MI(MIresultingindeathwhenbiomarkersarenotavailable)andtype4and5MI(relatedtopercutaneouscoronaryintervention[PCI]andcoronaryarterybypassgrafting[CABG],respectively).

2.1.2Unstableanginaintheeraofhigh-sensitivitycardiactroponinassays

Unstableanginaisde nedasmyocardialischaemiaatrestorminimalexertionintheabsenceofcardiomyocytenecrosis.Amongunse-lectedpatientspresentingwithsuspectedNSTE-ACStotheemer-gencydepartment,theintroductionofhigh-sensitivitycardiactroponinmeasurementsinplaceofstandardtroponinassaysresultedinanincreaseinthedetectionofMI( 4%absoluteand20%relativeincrease)andareciprocaldecreaseinthediagnosisofunstablean-gina.7–10ComparedwithNSTEMIpatients,individualswithunstableanginadonotexperiencemyocardialnecrosis,haveasubstantiallylowerriskofdeathandappeartoderivelessbene tfromintensi edantiplatelettherapyaswellasearlyinvasivestrategy.2–4,6–132.1.3Pathophysiologyandepidemiology(seeWebaddenda)

3.Diagnosis

3.1Clinicalpresentation

AnginalpaininNSTE-ACSpatientsmayhavethefollowingpresentations:

Prolonged(.20min)anginalpainatrest;

Newonset(denovo)angina(classIIorIIIoftheCanadianCar-diovascularSocietyclassi cation);21

RecentdestabilizationofpreviouslystableanginawithatleastCanadianCardiovascularSocietyClassIIIanginacharacteristics(crescendoangina);or Post-MIangina.

Prolongedanddenovo/crescendoanginaareobservedin 80%and 20%ofpatients,respectively.Typicalchestpainischaracter-izedbyaretrosternalsensationofpressureorheaviness(‘angina’)radiatingtotheleftarm(lessfrequentlytobotharmsortotherightarm),neckorjaw,whichmaybeintermittent(usuallylastingseveralminutes)orpersistent.Additionalsymptomssuchassweating,nau-sea,abdominalpain,dyspnoeaandsyncopemaybepresent.Atypical

Downloaded from http://www.77cn.com.cn/ by guest on August 30, 2015

2015ESC非ST段抬高心肌梗死治疗指南

isolateddyspnoea.Atypicalcomplaintsaremoreoftenobservedinmechanicalcomplication(i.e.papillarymuscleruptureorventriculartheelderly,inwomenandinpatientswithdiabetes,chronicrenalseptaldefect)ofasubacuteandpossiblyundetectedMI.Physicaldiseaseordementia.22–24Theexacerbationofsymptomsbyphys-examinationmayidentifysignsofnon-coronarycausesofchesticalexertionandtheirreliefatrestincreasetheprobabilityofmyo-pain(e.g.pulmonaryembolism,acuteaorticsyndromes,myoperi-cardialischaemia.Thereliefofsymptomsafternitratescarditis,aorticstenosis)orextracardiacpathologies(e.g.pneumo-administrationisnotspeci cforanginalpainasitisreportedalsothorax,pneumoniaormusculoskeletaldiseases).Inthissetting,inothercausesofacutechestpain.24Inpatientspresentingwithsus-thepresenceofachestpainthatcanbereproducedbyexertingpectedMItotheemergencydepartment,overall,thediagnosticper-pressureonthechestwallhasarelativelyhighnegativepredictiveformanceofchestpaincharacteristicsforMIislimited.24Olderage,valueforNSTE-ACS.24,26Accordingtothepresentation,abdominalmalegender,familyhistoryofCAD,diabetes,hyperlipidaemia,disorders(e.g.oesophagealspasm,oesophagitis,gastriculcer,chole-hypertension,renalinsuf ciency,previousmanifestationofCADcystitis,pancreatitis)mayalsobeconsideredinthedifferentialdiag-aswellasperipheralorcarotidarterydiseaseincreasethelikelihoodnosis.DifferencesinbloodpressurebetweentheupperandlowerofNSTE-ACS.Conditionsthatmayexacerbateorprecipitatelimbsorbetweenthearms,irregularpulse,jugularveindistension,NSTE-ACSincludeanaemia,infection,in ammation,fever,andheartmurmurs,frictionrubandpainreproducedbychestorab-metabolicorendocrine(inparticularthyroid)disorders.

dominalpalpationare ndingssuggestiveofalternativediagnoses.Pallor,sweatingortremormaypointtowardsprecipitatingcondi-3.2Physicalexamination

tionssuchasanaemiaandthyrotoxicosis.27

PhysicalexaminationisfrequentlyunremarkableinpatientswithsuspectedNSTE-ACS.Signsofheartfailureorhaemodynamicor3.3Diagnostictools

electricalinstabilitymandateaquickdiagnosisandtreatment.Car-3.3.1Electrocardiogram

diacauscultationmayrevealasystolicmurmurduetoischaemicmi-Theresting12-leadECGisthe rst-linediagnostictoolintheassess-tralregurgitation,whichisassociatedwithpoorprognosis,oraortic

mentofpatientswithsuspectedACS(Figure1).Itisrecommendedto

Downloaded from http://www.77cn.com.cn/ by guest on August 30, 2015

2015ESC非ST段抬高心肌梗死治疗指南

immediatereperfusion.1Comparisonwithprevioustracingsisvaluable,particularlyinpatientswithpre-existingECGabnormal-ities.Itisrecommendedtoobtainadditional12-leadECGsinthecaseofpersistentorrecurrentsymptomsordiagnosticuncer-tainty.Inpatientswithbundlebranchblockorpacedrhythm,ECGisofnohelpforthediagnosisofNSTE-ACS.

3.3.2Biomarkers

Biomarkerscomplementclinicalassessmentand12-leadECGinthediagnosis,riskstrati cationandtreatmentofpatientswithsuspectedNSTE-ACS.Measurementofabiomarkerofcardiomyocyteinjury,preferablyhigh-sensitivitycardiactroponin,ismandatoryinallpa-tientswithsuspectedNSTE-ACS.2,6,8Cardiactroponinsaremoresensitiveandspeci cmarkersofcardiomyocyteinjurythancreatinekinase(CK),itsMBisoenzyme(CK-MB)andmyoglobin.6Iftheclin-icalpresentationiscompatiblewithmyocardialischaemia,thenady-namicelevationofcardiactroponinabovethe99thpercentileofhealthyindividualsindicatesMI.2InpatientswithMI,levelsofcardiactroponinriserapidly(http://www.77cn.com.cnuallywithin1hifusinghigh-sensitivityas-says)aftersymptomonsetandremainelevatedforavariableperiodoftime(usuallyseveraldays).2,6Advancesintechnologyhaveledtoare nementincardiactroponinassaysandhaveimprovedtheabilitytodetectandquantifycardiomyocyteinjury.2,6,8,10,29–37InEurope,

recommendedoverlesssensitiveones.2,6,8Themajorityofcurrentlyusedpoint-of-careassayscannotbeconsideredsensitiveorhigh-sensitivityassays.8,35Thereforetheobviousadvantageofpoint-of-caretests,namelytheshorterturnaroundtime,iscounter-balancedbylowersensitivity,lowerdiagnosticaccuracyandlowernegativepredictivevalue.Overall,automatedassayshavebeenmorethoroughlyevaluatedascomparedwithpoint-of-caretests.2,6,8Asthesetechniquescontinuetoimproveandperformancecharac-teristicsarebothassayandhospitaldependent,norecommendationregardingthesiteofmeasurement(centrallaboratoryvs.bedside)canbegiven.2,6,8,38Datafromlargemulticentrestudieshaveconsist-entlyshownthatsensitiveandhigh-sensitivitycardiactroponinas-saysincreasediagnosticaccuracyforMIatthetimeofpresentationascomparedwithconventionalassays,especiallyinpatientspresent-ingearlyafterchestpainonset,andallowforamorerapid‘rule-in’and‘rule-out’ofMI(seesection3.3.3andTable3).2,6,8,29–34

Inmostpatientswithrenaldysfunction,elevationsincardiactropo-ninshouldnotbeprimarilyattributedtoimpairedclearanceandcon-sideredharmless,ascardiacconditionssuchaschroniccoronaryorhypertensiveheartdiseaseseemtobethemostimportantcontribu-tortotroponinelevationinthissetting.41Otherlife-threateningcon-ditionspresentingwithchestpain,suchasaorticdissectionandpulmonaryembolism,mayalsoresultinelevatedtroponinlevelsandshouldbeconsideredasdifferentialdiagnoses(Table4).

Downloaded from http://www.77cn.com.cn/ by guest on August 30, 2015

2015ESC非ST段抬高心肌梗死治疗指南

Amongthemultitudeofadditionalbiomarkersevaluatedforthe

diagnosisofNSTE-ACS,onlyCK-MBandcopeptinseemtohaveclinicalrelevance.2,6,8,10,44–50CK-MBshowsamorerapiddeclineafterMIascomparedwithcardiactroponinandmayprovideaddedvalueforthetimingofmyocardialinjuryandthedetectionofearlyreinfarction.2,6,8,10Assessmentofcopeptin,theC-terminalpartofthevasopressinprohormone,mayquantifytheendogenousstresslevelinmultiplemedicalconditionsincludingMI.Asthelevelofen-dogenousstressappearstobeinvariablyhighattheonsetofMI,theaddedvalueofcopeptintoconventional(lesssensitive)cardiactroponinassaysissubstantial.44–50Thereforetheroutineuseofcopeptinasanadditionalbiomarkerfortheearlyrule-outofMIisrecommendedwheneversensitiveorhigh-sensitivitycardiactroponinassaysarenotavailable.Copeptinmayhavesomeaddedvalueevenoverhigh-sensitivitycardiactroponinintheearlyrule-outofMI.44–48

3.3.3‘Rule-in’and‘rule-out’algorithms

Duetothehighersensitivityanddiagnosticaccuracyforthedetec-tionofacuteMIatpresentation,thetimeintervaltothesecondcar-diactroponinassessmentcanbeshortenedwiththeuseofhigh-sensitivityassays.Thismayreducesubstantiallythedelaytodiagnosis,translatingintoshorterstaysintheemergencydepart-mentandlowercosts.2,6,8,10,29–36Itisrecommendedtousethe0h/3halgorithm(Figure2).Asanalternative,0h/1hassessmentsarerecommendedwhenhigh-sensitivitycardiactroponinassayswithavalidatedalgorithmareavailable(Figure3).The0h/1halgo-rithmsrelyontwoconcepts: rst,high-sensitivitycardiactroponinisacontinuousvariableandtheprobabilityofMIincreaseswithin-absolutechangesover3hor6handprovideincrementaldiagnosticcreasinghigh-sensitivitycardiactroponinvalues;39second,earlyab-valuetothecardiactroponinassessmentatpresentation.39Thecut-solutechangesofthelevelswithin1hcanbeusedassurrogatesfor

offlevelswithinthe0h/1halgorithmareassayspeci c.36,39,51–55

Downloaded from http://www.77cn.com.cn/ by guest on August 30, 2015

2015ESC非ST段抬高心肌梗死治疗指南

ESCGuidelines

Thosealgorithmsshouldalwaysbeintegratedwithadetailedclinicalassessmentand12-leadECGandrepeatbloodsamplingismandatoryincaseofongoingorrecurrentchestpain(Table5,seeWebaddenda).

Table5(seeWebaddenda)Characteristicsofthe0h/3hand0h/1halgorithms

ThenegativepredictivevalueforMIinpatientsassigned‘rule-out’exceeded98%inseverallargevalidationcohorts.30–34,36,39,51–55UsedinconjunctionwithclinicalandECG ndings,the0h/1halgorithmmayallowtheidenti cationofcandidatesforearlydis-chargeandoutpatientmanagement.ThepositivepredictivevalueforMIinthosepatientsmeetingthe‘rule-in’criteriawas75–80%.30–34,39,53–55Mostofthe‘rule-in’patientswithdiagnosesotherthanMIdidhaveconditionsthatusuallyrequireinpatientcoronaryangiographyforaccuratediagnosis,includingTako–Tsubocardio-myopathyandmyocarditis.39,53–55Patientswhodonotqualifyfor‘rule-out’or‘rule-in’representaheterogeneousgroupthatmayre-quirefurtherinvestigationsifnoalternativeexplanationforthecar-diactroponinelevationisidenti ed.Alargeproportionofthesepatientsmayrequireafurtherhigh-sensitivitycardiactroponinas-sessment(e.g.at3h).CoronaryangiographyshouldbeconsideredinpatientsforwhomthereisahighdegreeofclinicalsuspicionofNSTE-ACS,whileinpatientswithlowtointermediatelikelihoodforthiscondition,computedtomography(CT)coronaryangiog-raphyshouldbeconsidered.Nofurtherdiagnostictestingintheemergencydepartmentisindicatedwhenalternativeconditionssuchasrapidventricularrateresponsetoatrial brillationorhyper-tensiveemergencyhavebeenidenti ed.

Forrapidrule-out,twoalternativeapproachestothe0h/1hor0h/3halgorithmshavebeenadequatelyvalidatedandmaybeconsidered.First,a2hrule-outprotocolcombiningtheThromboly-sisinMyocardialInfarction(TIMI)riskscorewithECGandhigh-sensitivitycardiactroponinatpresentationallowedasaferule-outinupto40%ofpatients.56–58Second,adual-markerstrategycom-biningnormallevelsofcardiactroponintogetherwithlowlevelsofcopeptin(,10pmol/L)atpresentationshowedveryhighnegativepredictivevalueforMI,obviatingtheneedforserialtestinginse-lectedpatients.44–50Whenusinganyalgorithm,threemaincaveatsapply:(i)algorithmsshouldonlybeusedinconjunctionwithallavail-ableclinicalinformation,includingdetailedassessmentofchestpaincharacteristicsandECG;(ii)inpatientspresentingveryearly(e.g.within1hfromchestpainonset),thesecondcardiactroponinlevelshouldbeobtainedat3h,duetothetimedependencyoftroponinrelease;(iii)aslateincreasesincardiactroponinhavebeende-scribedin 1%ofpatients,serialcardiactroponintestingshouldbepursuediftheclinicalsuspicionremainshighorwheneverthepa-tientdevelopsrecurrentchestpain.52,54High-sensitivitycardiactroponinassaysalsomaintainhighdiagnosticaccuracyinpatientswithrenaldysfunction.Toensurethebestpossibleclinicaluse,assay-speci coptimalcut-offlevels,whicharehigherinpatientswithrenaldysfunction,shouldbeused.593.3.4Non-invasiveimaging

3.3.4.1Functionalevaluation

Transthoracicechocardiographyshouldberoutinelyavailableinemergencyroomsandchestpainunitsandperformed/interpreted

Page11of59

bytrainedphysiciansinallpatientsduringhospitalizationforNSTE-ACS.Thisimagingmodalityisusefultoidentifyabnormalitiessuggestiveofmyocardialischaemiaornecrosis(i.e.segmentalhypo-kinesiaorakinesia).Intheabsenceofsigni cantwallmotionabnor-malities,impairedmyocardialperfusiondetectedbycontrastechocardiographyorreducedregionalfunctionusingstrainandstrainrateimagingmightimprovethediagnosticandprognosticva-lueofconventionalechocardiography.60,61Moreover,echocardiog-raphycanhelpindetectingalternativepathologiesassociatedwithchestpain,suchasacuteaorticdissection,pericardialeffusion,aorticvalvestenosis,hypertrophiccardiomyopathyorrightventriculardilatationsuggestiveofacutepulmonaryembolism.Similarly,echo-cardiographyisthediagnostictoolofchoiceforpatientswithhaemodynamicinstabilityofsuspectedcardiacorigin.62Evaluationofleftventricular(LV)systolicfunction,atthelatestbythetimeofhospitaldischarge,isimportanttoestimateprognosis,andecho-cardiography(aswellasotherimagingmodalities)canprovidethisinformation.

Inpatientswithoutischaemicchangeson12-leadECGsandnega-tivecardiactroponins(preferablyhigh-sensitivity)whoarefreeofchestpainforseveralhours,stressimagingcanbeperformedduringadmissionorshortlyafterdischarge.StressimagingispreferredoverexerciseECGduetoitsgreaterdiagnosticaccuracy.63Variousstudieshaveshownthatnormalexercise,dobutamineordipyridamolestressechocardiogramshavehighnegativepredictivevalueforischaemiaandareassociatedwithexcellentpatientoutcomes.64,65Moreover,stressechocardiographydemonstratedsuperiorprognosticvalueoverexer-ciseECG.64,66Theadditionofcontrastmayimproveendocardialbor-derdetection,whichmayfacilitatedetectionofischaemia.67

Cardiacmagneticresonance(CMR)canassessbothperfusionandwallmotionabnormalities,andpatientspresentingwithacutechestpainwithanormalstressCMRhaveanexcellentshort-andmidtermprognosis.68CMRalsopermitsdetectionofscartissue(usinglategadoliniumenhancement)andcandifferentiatethisfromrecentinfarction(usingT2-weightedimagingtodelineatemyo-cardialoedema).69,70Moreover,CMRcanfacilitatethedifferentialdiagnosisbetweeninfarctionandmyocarditisorTako–Tsubocar-diomyopathy.71Similarly,nuclearmyocardialperfusionimaginghasbeenshowntobeusefulforriskstrati cationofpatientswithacutechestpainsuggestiveforACS.Restingmyocardialscintigraphy,bydetecting xedperfusiondefectssuggestiveofmyocardialnecrosis,canbehelpfulforinitialtriageofpatientspresentingwithchestpainwithoutECGchangesorelevatedcardiactroponins.72Combinedstress–restimagingmayfurtherenhanceassessmentofischaemia,whileanormalstudyisassociatedwithexcellentoutcome.73,74Stress–restimagingmodalitiesareusuallynotwidelyavailableon24hservice.

3.3.4.2Anatomicalevaluation

Multidetectorcomputedtomography(MDCT)allowsforvisualiza-tionofthecoronaryarteriesandanormalscanexcludesCAD.Ameta-analysisofninestudies(n¼1349patients)hasreportedover-allhighnegativepredictivevaluestoexcludeACS(byexcludingCAD)andexcellentoutcomeinpatientspresentingtotheemer-gencydepartmentwithlowtointermediatepre-testprobabilityforACSandanormalcoronaryCTangiogram.75Fourrandomizedcontrolledtrials(RCTs)havetestedMDCT(n¼1869patients)vs.

Downloaded from http://www.77cn.com.cn/ by guest on August 30, 2015

2015ESC非ST段抬高心肌梗死治疗指南

Page12of59

ESCGuidelines

usualcare(n¼1397)inthetriageoflow-tointermediate-riskpa-andcoronaryarteryspasmarebrie ydescribedinsection5.6.4.2,tientspresentingwithacutechestpaintoemergencydepartmentsWebaddenda.StrokemaybeaccompaniedbyECGchanges,myo-withoutsignsofischaemiaonECGand/orinconclusivecardiactro-cardialwallmotionabnormalitiesandanincreaseincardiactroponinponins.76–79Atafollow-upof1–6months,therewerenodeaths,levels.2,6Themajorityofpatientspresentingwithacutechestpaintoandameta-analysisdemonstratedcomparableoutcomeswiththetheemergencydepartmenthavenon-cardiacconditionscausingthetwoapproaches(i.e.nodifferenceintheincidenceofMI,post-chestdiscomfort.Inmanyinstancesthepainismusculoskeletal,anddischargeemergencydepartmentvisitsorrehospitalizations)andthereforebenign,self-limitinganddoesnotrequirehospitalization.showedthatMDCTwasassociatedwithareductioninemergencyde-Chestpaincharacteristicshelptosomeextentintheearlyidenti ca-partmentcostsandlengthofstay.80However,noneofthesestudiestionofthosepatients.24

usedhigh-sensitivitycardiactroponinassays,whichalsomayreducehospitalstay.ItwasalsonotedthatMDCTwasassociatedwithanin-creaseintheuseofinvasiveangiography{8.4%vs.6.3%;oddsratio4.Riskassessmentandoutcomes

[OR]1.36[95%con denceinterval(CI)1.03,1.80],P¼0.030}.80Ac-cordingly,MDCTcoronaryangiographycanbeusedtoexcludeCAD4.1Clinicalpresentation,

(andMDCTisthusnotusefulinpatientswithknownCAD).OtherfactorslimitingMDCTcoronaryangiographyincludeseverecalci ca-electrocardiogramandbiomarkers

tions(highcalciumscore)andelevatedorirregularheartrate;inadd-4.1.1Clinicalpresentation

ition,asuf cientlevelofexpertiseisneededand24hserviceisInadditiontosomeuniversalclinicalmarkersofrisk,suchasad-currentlynotwidelyavailable.Finally,theuseofMDCTcoronaryangi-vancedage,diabetesandrenalinsuf ciency,theinitialclinicalpres-ographyintheacutesettinginpatientswithstentsorpreviousCABGentationishighlypredictiveofearlyprognosis.82Chestpainatresthasnotbeenvalidated.Importantly,CTimagingcaneffectivelyexcludecarriesaworseprognosisthansymptomselicitedduringphysicalothercausesofacutechestpainthat,ifuntreated,areassociatedwithexertion.Inpatientswithintermittentsymptoms,anincreasinghighmortality,namelypulmonaryembolism,aorticdissectionandten-numberofepisodesprecedingtheindexeventalsoadverselyaffectssionpneumothorax.81

prognosis.Tachycardia,hypotension,heartfailureandnewmitralregurgitationatpresentationpredictpoorprognosisandcallforra-3.4Differentialdiagnosis

piddiagnosisandmanagement.25,82–84

Amongunselectedpatientspresentingwithacutechestpaintothe4.1.2Electrocardiogram

emergencydepartment,diseaseprevalencecanbeexpectedtobeTheinitialECGispredictiveofearlyrisk.18PatientswithSTdepres-thefollowing:5–10%STEMI,15–20%NSTEMI,10%unstablean-sionhaveaworseprognosisthanpatientswithanormalECG.85,86gina,15%othercardiacconditionsand50%non-cardiacdis-ThenumberofleadsshowingSTdepressionandthemagnitudeofeases.48,51,52,56–58Severalcardiacandnon-cardiacconditionsmaySTdepressionareindicativeoftheextentofischaemiaandcorrelatemimicNSTE-ACS(Table6).

withprognosisontheonehand,andbene tfromaninvasivetreat-Conditionsthatshouldalwaysbeconsideredinthedifferentialmentstrategyontheother.87STdepression≥0.05mVintwoordiagnosisofNSTE-ACS,becausetheyarepotentiallylife-morecontiguousleads,intheappropriateclinicalcontext,issug-threateningbutalsotreatable,includeaorticdissection,pulmonarygestiveofNSTE-ACSandlinkedtoadverseprognosis.85STdepres-embolismandtensionpneumothorax.EchocardiographyshouldbesioncombinedwithtransientSTelevationidenti esahigh-riskperformedurgentlyinallpatientswithhaemodynamicinstabilityofsubgroup,88whileassociatedT-waveinversiondoesnotalterthesuspectedcardiovascular(CV)origin.62

prognosticvalueofSTdepression.WhileisolatedT-waveinversionChestX-rayisrecommendedinallpatientsinwhomNSTE-ACSisonadmissionhasnotbeenassociatedwithworseprognosiscom-consideredunlikelyinordertodetectpneumonia,pneumothorax,ribparedwiththeabsenceofECGabnormalities,itfrequentlytriggersfracturesorotherthoracicdisorders.Tako–Tsubocardiomyopathyamorerapiddiagnosisandtreatment.86

Downloaded from http://www.77cn.com.cn/ by guest on August 30, 2015

2015ESC非ST段抬高心肌梗死治疗指南

ESCGuidelines

4.1.3Biomarkers

Beyonddiagnosticutility,cardiactroponinlevelsaddprognosticin-formationintermsofshort-andlong-termmortalitytoclinicalandECGvariables.Whilehigh-sensitivitycardiactroponinTandIseemtohavecomparablediagnosticaccuracy,high-sensitivitycardiactroponinThasgreaterprognosticaccuracy.89,90Thehigherthehigh-sensitivitytroponinlevelsatpresentation,thegreatertheriskofdeath.6,8,10,39MultiplebiomarkershavebeenassociatedwithmortalityinNSTE-ACS,severalofthemconferringadditiveprognosticvaluetocardiactroponin.8,48–50Serumcreatinineandestimatedglomerular ltrationrate(eGFR)shouldalsobedeter-minedinallpatientswithNSTE-ACSbecausetheyaffectprognosisandarekeyelementsoftheGlobalRegistryofAcuteCoronaryEvents(GRACE2.0)riskcalculation(seesection4.2).Theexten-sivelyvalidatednatriureticpeptides(i.e.B-typenatriureticpeptide,N-terminalpro-B-typenatriureticpeptideandmidregionalpro-A-typenatriureticpeptide)provideprognosticinformationontopofcardiactroponin.91Tosomeextent,thesameappliestohigh-sensitivityC-reactiveproteinandnovelbiomarkerssuchasmidre-gionalpro-adrenomedullin,growthdifferentiationfactor15andcopeptin.However,theassessmentofthesemarkershassofarnotbeenshowntoimprovepatientmanagementandtheiraddedvalueinriskassessmentontopoftheGRACE2.0riskcalculationseemsmarginal.Thereforetheroutineuseofthesebiomarkersforprognos-ticpurposescannotberecommendedatthepresenttime.

4.2Ischaemicriskassessment

InNSTE-ACS,quantitativeassessmentofischaemicriskbymeansofscoresissuperiortotheclinicalassessmentalone.TheGRACEriskscoreprovidesthemostaccuratestrati cationofriskbothonad-missionandatdischarge.92,93TheGRACE2.0riskcalculator(http://www.77cn.com.cn/WebSite/default.aspx?ReturnUrl=%2f)pro-videsadirectestimation,bypassingthecalculationofascore,ofmortalitywhileinhospital,at6months,at1yearandat3years.ThecombinedriskofdeathorMIat1yearisalsoprovided.94VariablesusedintheGRACE2.0riskcalculationincludeage,systolicbloodpressure,pulserate,serumcreatinine,Killipclassatpresenta-tion,cardiacarrestatadmission,elevatedcardiacbiomarkersandSTdeviation.IftheKillipclassorserumcreatininevaluesarenotavail-able,amodi edscorecanbecalculatedbyaddingrenalfailureanduseofdiuretics,respectively.TheTIMIriskscoreusessevenvari-ablesinanadditivescoringsystem:age≥65years,threeormoreCADriskfactors,knownCAD,aspirinuseinthepast7days,severeangina(twoormoreepisodeswithin24h),STchange≥0.5mmandpositivecardiacmarker(http://www.77cn.com.cn/index.php?page=calculators).82Itissimpletouse,butitsdiscriminativeaccuracyisin-feriortothatoftheGRACEriskscoreandtheGRACE2.0riskcal-culation.Whilethevalueofriskscoresasprognosticassessmenttoolsisundisputed,theimpactofriskscoreimplementationonpa-tientoutcomeshasnotbeenadequatelyinvestigated.95,96

4.2.1Acuteriskassessment

PatientswithsuspectedNSTE-ACSmustbeevaluatedrapidlyinordertoidentifyindividualswithongoingmyocardialischaemiawhoareatriskoflife-threateningarrhythmiasandneedclosesurveillanceaswellasimmediatecoronaryangiography.PatientswithsuspectedNSTE-ACSshouldbeobservedininterdisciplinaryemergencydepart-mentsorchestpainunitsuntilthediagnosisofMIiscon rmedorruled

Page13of59

out.ThegreatestchallengeistheintegrationofclinicalpresentationwithinformationderivedfromECG,troponinassessmentandimagingmodalitiesintoastandardisedmanagementstrategy.97Assessmentofacuteriskguidesinitialevaluation,selectionofthesiteofcare(i.e.cor-onaryorintensivecareunit,intermediatecareunit,inpatientmoni-toredunitorregularunit)andtherapy,includingantithrombotictreatmentandtimingofcoronaryangiography.Riskishighestatthetimeofpresentationandmayremainelevatedforseveraldays,al-thoughrapidlydecliningovertime,dependingonclinicalpresentation,comorbidities,coronaryanatomyandrevascularization.98Theesti-matedriskshouldbecommunicatedtothepatientandtheirfamily.

4.2.2Cardiacrhythmmonitoring

Earlyrevascularizationaswellastheuseofantithromboticagentsandbeta-blockershavemarkedlyreducedtheincidenceoflife-threateningarrhythmiasintheacutephaseto,3%,withmostofthearrhythmiceventsoccurringwithin12hofsymptomon-set.99,100Patientswithlife-threateningarrhythmiasmorefrequentlyhadpriorheartfailure,LVejectionfraction(LVEF),30%andtriple-vesselCAD.ApatientwithNSTE-ACSwhopresentsearlyaftersymptomonset,hasnoormildtomoderatecardiacbiomarkerele-vation,normalLVfunctionandsingle-vesselCADsuccessfullytrea-tedwithPCImaybedischargedthenextday.AttheotherendofthespectrumareNSTE-ACSpatientswithmultivesselCADinwhomcompleterevascularizationmaynotbeachievedinonesession(oratall);thesepatientsmayhaveacomplicatedcourse(e.g.heartfailure)orpriorcardiacdisease,majorcomorbidities,advancedageorrecentextensivemyocardialnecrosis.101,102Cardiactroponin-negative(i.e.unstableangina)patientswithoutrecurrentorongoingsymptomsandwithnormalECGdonotnecessarilyrequirerhythmmonitoringorhospitaladmission.

NSTEMIpatientsatlowriskforcardiacarrhythmiasrequirerhythmmonitoringfor≤24horuntilcoronaryrevascularization(whichevercomes rst)inanintermediateorcoronarycareunit,whileindividualsatintermediatetohighriskforcardiacarrhythmiamayrequirerhythmmonitoringfor.24hinanintensiveorcoronarycareunitorinanintermediatecareunit,dependingontheclinicalpresentation,degreeofrevascularizationandearlypost-revascularizationcourse(Table7).Itisrecommendedthatper-sonneladequatelyequippedandtrainedtomanagelife-threateningDownloaded from http://www.77cn.com.cn/ by guest on August 30, 2015

2015ESC非ST段抬高心肌梗死治疗指南

Page14of59

arrhythmiasandcardiacarrestaccompanypatientswhoaretrans-ferredbetweenfacilitiesduringthetimewindowinwhichtheyre-quirecontinuousrhythmmonitoring.

4.2.3Long-termrisk

Inadditiontoshort-termriskfactors,anumberofconditionsareas-sociatedwithlong-termrisk,includingacomplicatedclinicalcourse,LVsystolicdysfunction,atrial brillation,severityofCAD,revascu-larizationstatus,evidenceofresidualischaemiaonnon-invasivetest-ingandnon-cardiaccomorbidities.At1year,theratesofdeath,MIandrecurrentACSincontemporaryNSTE-ACSregistriesare.10%.Whileearlyeventsarerelatedtorupturedcoronaryplaquesandassociatedthrombosis,themajorityoflatereventsmaybetheresultofcoronaryandsystemicatherosclerosisprogression.98,103

4.3Bleedingriskassessment

MajorbleedingeventsareassociatedwithincreasedmortalityinNSTE-ACS.104,105BleedingriskscoreshavebeendevelopedfromregistryortrialcohortsinthesettingofACSandPCI.TheCanRapidriskstrati cationofUnstableanginapatientsSuppressADverseoutcomeswithEarlyimplementationoftheACC/AHAguidelines(CRUSADE)bleedingriskscore(http://www.77cn.com.cn)wasdevelopedfromacohortof71277NSTE-ACSpatients(derivationcohort)andfurthervalidatedinaco-hortof17857patients(validationcohort)fromthesameregistry.106TheCRUSADEbleedingriskscoreconsideredbaselinepatientchar-acteristics(i.e.femalegender,historyofdiabetes,historyofperipheralvasculardiseaseorstroke),admissionclinicalvariables(i.e.heartrate,systolicbloodpressure,signsofheartfailure)andadmissionlabora-toryvalues(i.e.haematocrit,calculatedcreatinineclearance)toesti-matethepatient’slikelihoodofanin-hospitalmajorbleedingevent.However,modelperformancefortheriskscorewasmodest(C-statistic0.68inpatientstreatedconservativelyand0.73inpatientsundergoinginvasiveapproach).

TheAcuteCatheterizationandUrgentInterventionTriagestrat-egY(ACUITY)bleedingriskscorewasderivedfromapooledcohortof17421patientswithACS(bothNSTE-ACSandSTEMI)recruitedintheACUITYandHarmonizingOutcomeswithRevasculariZatiONandStentsinAcuteMyocardialInfarction(HORIZONS-AMI)trials.104Sixindependentbaselinepredictors(i.e.femalegender,advancedage,elevatedserumcreatinine,whitebloodcellcount,anaemiaandpresentationasNSTEMIorSTEMI)andonetreat-ment-relatedvariable[useofunfractionatedheparin(UFH)andaglycoproteinIIb/IIIa(GPIIb/IIIa)inhibitorratherthanbivalirudinalone]wereidenti ed.Thisriskscoreidenti edpatientsatincreasedriskfornon-CABG-relatedmajorbleedsat30daysandsubsequent1yearmortality.However,ithasnotbeenvalidatedinanindependentco-hort,noriskcalculatorisavailableandmodelperformancefortheriskscoreismodest(C-statistic0.74).Changesininterventionalpractice,suchasincreasinguseofradialaccess,reductioninthedoseofUFH,useofbivalirudin,diminisheduseofGPIIb/IIIainhibitorsandadminis-trationofmoreeffectiveinhibitorsoftheplateletadenosinediphos-phate(ADP)receptorP2Y12(P2Y12inhibitors),mayallmodifythepredictivevalueofriskscores.Ischaemicandbleedingrisksneedtobeweighedintheindividualpatient,althoughmanyofthepredictorsofischaemiceventsarealsoassociatedwithbleedingcomplica-tions.104,106Overall,CRUSADEandACUITYscoreshavereasonablepredictivevalueformajorbleedinginACSpatientsundergoing

ESCGuidelines

coronaryangiography,withCRUSADEfoundtobethemostdiscrim-inatory.107However,inpatientsmedicallytreatedoronoralanticoa-gulants,thepredictivevalueofthesescoresisnotestablished.Moreover,theimpactonpatientoutcomesofintegratingthesescoreshasnotbeeninvestigated.Giventheselimitations,useoftheCRUSADEbleedingriskscoremaybeconsideredinpatientsunder-goingcoronaryangiographytoquantifybleedingrisk.

4.4Recommendationsfordiagnosis,riskstrati cation,imagingandrhythmmonitoringinpatientswithsuspectednon-ST-elevationacutecoronarysyndromes

Downloaded from http://www.77cn.com.cn/ by guest on August 30, 2015

2015ESC非ST段抬高心肌梗死治疗指南

Downloaded from http://www.77cn.com.cn/ by guest on August 30, 2015

2015ESC非ST段抬高心肌梗死治疗指南

Page16of59

5.1.4Otherdrugclasses(seeWebaddenda)

5.1.5Recommendationsforanti-ischaemicdrugsintheacutephaseofnon-ST-elevationacutecoronarysyndromes5.2Plateletinhibition

5.2.1Aspirin

Aspirin(acetylsalicylicacid)irreversiblyinactivatesthecyclooxygen-ase(COX)activityofplateletprostaglandinendoperoxide(PGH)synthase1(COX-1),therebysuppressingthromboxaneA2pro-ductionthroughouttheplateletlifespan.128Aspirinhasbeenshowntobeeffectiveinpatientswithunstableangina;theincidenceofMIordeathwasconsistentlyreducedinfourRCTsinthepre-PCIera.129–132Ameta-analysisofthesetrialssuggeststhataspirinadministration(upto2years)isassociatedwithahighlysig-ni cant46%oddsreductioninmajorvascularevents.133TheClopi-dogrelandAspirinOptimalDoseUsagetoReduceRecurrentEvents–SeventhOrganizationtoAssessStrategiesinIschaemicSyn-dromes(CURRENT-OASIS7),whichenrolled25086ACS(bothNSTE-ACSandSTEMI)patientsundergoinginvasivestrategy,foundnodifferencebetweenhigher-dose(300–325mg/day)andlower-dose(75–100mg/day)aspirin.134Anoralloadingdose(150–300mg)ofplainaspirin(non-enteric-coatedformulation)isrecom-mended,whiletherecommendedintravenous(i.v.)doseis150mg.Nomonitoringofitseffectsisrequired.ThemechanismsofactionofantiplateletandanticoagulantagentsaredescribedinFigure4.5.2.2P2Y12inhibitors5.2.2.1Clopidogrel

Clopidogrel(300–600mgloadingand75mg/daymaintenancedose)isaninactiveprodrugthatrequiresoxidationbythehepatic

ESCGuidelines

cytochromeP450(CYP)systemtogenerateanactivemetabolite(Ta-ble8).Anestimated85%oftheprodrugishydrolysedbyesterasesintoaninactiveform,leavingonly15%ofclopidogrelavailablefortransformationtotheactivemetabolite,whichselectivelyandirre-versiblyinactivatesplateletP2Y12receptorsandthusinhibitsADP-inducedplateletaggregation.135,136Dualantiplatelettherapy(DAPT)comprisingaspirinandclopidogrelhasbeenshowntoreducerecurrentischaemiceventsintheNSTE-ACSsettingcomparedwithaspirinalone.137,138However,upto10%ofpatientstreatedwiththecombinationofaspirinandclopidogrelwillhavearecurrentischaemiceventinthe rstyearafteranACS,witharateofstentthrombosisofupto2%.139Thisresidualriskmaybepartlyexplainedbysuboptimalplateletinhibitionduetoinadequateresponsetoclopidogrel.Indeed,pharmacodynamicandpharmacokineticstudieshavedescribedsub-stantialinterindividualvariabilityintheantiplateletresponsetothisdrugandanincreasedriskofischaemicandbleedingeventsinclopi-dogrelhypo-andhyper-responders,respectively.140–143Thereisevi-dencethatkeygenepolymorphismsareinvolvedinboththevariabilityofactivemetabolitegenerationandclinicalef cacyofclo-pidogrel.144–147

5.2.2.2Prasugrel

Prasugrel(60mgloadingand10mg/daymaintenancedose)isapro-drugthatirreversiblyblocksplateletP2Y12receptorswithafasteronsetandamoreprofoundinhibitoryeffectthanclopidogrel(Table8).Thiscompoundhasbeentestedagainstthe300mgload-ingand75mg/daymaintenancedoseofclopidogrelintheTRialtoAssessImprovementinTherapeuticOutcomesbyOptimizingPlateletInhibitioNwithPrasugrel–ThrombolysisInMyocardialInfarction(TRITON-TIMI38),inwhichACSpatients(STEMIandNSTE-ACS)scheduledforPCIreceivedthedrugsduringoraftertheprocedure.148Inthe10074NSTE-ACSpatientsincluded,recur-rentCVeventswerereducedinprasugrel-treatedpatientsatthe15-monthfollow-up[from11.2%to9.3%;relativerisk(RR)0.82(95%CI0.73,0.93),P¼0.002],drivenbyasigni cantreductioninMI[from9.2%to7.1%;RRR23.9%(95%CI12.7,33.7),P,0.001].Severebleedingcomplicationsweremorecommonwithprasugrel[TIMInon-CABGmajorbleeds2.4%vs.1.8%;hazardratio(HR)1.40(95%CI1.05,1.88),P¼0.02],duetoanincreaseinspon-taneousbleeds[1.6%vs.1.1%;HR1.51(95%CI1.09,2.08),P¼0.01]andfatalbleeds[0.4%vs.0.1%;HR4.19(95%CI1.58,11.11),P¼0.002].149Bleedingeventswereincreasedbymorethanfour-foldinprasugrel-treatedpatientsreferredforearlyCABG.Basedonthemarkedreductioninde niteorprobablestentthrombosisobservedintheTRITON-TIMI38overall[1.13%intheprasugrelarmvs.2.35%intheclopidogrelarm;HR0.48(95%CI0.36,0.64),P,0.0001]andinpatientswithdrug-elutingstents(DESs)[0.84%vs.2.31%,respectively;HR0.36(95%CI0.22,0.58),P,0.0001],prasugrelshouldbeconsideredinpatientswhopresentwithstentthrombosisdespitecompliancewithclo-pidogreltherapy.150,151Prasugreliscontraindicatedinpatientswithpriorstroke/transientischaemicattack(TIA)duetoevidenceofnetharminthisgroupinTRITON-TIMI38.Inaddition,thestudyshowednoapparentbene tinpatients.75yearsofageorwithlowbodyweight(,60kg).148TheTargetedPlateletInhib-itiontoClarifytheOptimalStrategytoMedicallyManageAcuteCoronarySyndromes(TRILOGYACS)trialisdiscussedinsection5.6.4.1.1.

Downloaded from http://www.77cn.com.cn/ by guest on August 30, 2015

2015ESC非ST段抬高心肌梗死治疗指南

ESCGuidelines

Page17of59

ADP = adenosine diphosphate; AT = antithrombin; GP = glycoprotein; LMWH = low molecular weight heparin; Tx = thromboxane;UFH = Unfractionated heparin. Vorapaxar is a protease-activated receptor 1 (PAR1) blocker.

Figure4Antithromboticdrugsfornon-ST-elevationacutecoronarysyndromes.The guredepictsthetargetsofavailableantithrombotic

drugsthatcanbeusedtoinhibitbloodcoagulationandplateletaggregationduringandafterthrombusformation.

5.2.2.3Ticagrelor

drugsmetabolizedthroughCYP3A,suchassimvastatin,whilemod-Ticagrelorisanoral,reversiblybindingP2Y12inhibitorwithaplasmaerateCYP3Ainhibitors,suchasdiltiazem,increaseticagrelorplasmahalf-lifeof6–12h.Ticagreloralsoinhibitsadenosinereuptakevialevelsandmightdelaytheoffsetofeffect.InthePLATeletinhibitionequilabrativenucleosidetransporter1(ENT1)(Table8).Likeprasu-andpatientOutcomes(PLATO)trial,18624patientswithgrel,ticagrelorhasamorerapidandconsistentonsetofactioncom-moderate-tohigh-riskNSTE-ACS(plannedforeitherconservativeparedwithclopidogrel,aswellasafasteroffsetofactionwithmoreorinvasivemanagement)orSTEMIwererandomizedtoeitherclo-rapidrecoveryofplateletfunction.152Ticagrelorincreaseslevelsofpidogrel75mg/day,withaloadingdoseof300–600mg,

or

Downloaded from http://www.77cn.com.cn/ by guest on August 30, 2015

2015ESC非ST段抬高心肌梗死治疗指南

ticagrelor180mgloadingdosefollowedby90mgtwiceaday.1535.2.2.4Cangrelor

PatientsundergoingPCIwereallowedtoreceiveanadditionalCangrelorisani.v.adenosinetriphosphate(ATP)analoguethatbindsblinded300mgloadingdoseofclopidogrel(totalloadingdosereversiblyandwithhighaf nitytotheplateletP2Y12receptorandhas600mg)oritsplacebo.Treatmentwascontinuedforupto12ashortplasmahalf-life(,10min)(Table8).Itproducesahighlyef-months,withamediandurationofdrugexposureof9months.153fectiveinhibitionofADP-inducedplateletaggregationimmediatelyIntheNSTE-ACSsubgroup(n¼11080),theprimarycompositeef-afteri.v.bolusadministrationandallowsforrestorationofplatelet cacyendpoint(deathfromCVcauses,MIorstroke)wassigni -functionwithin1–2hofinfusiondiscontinuationinNSTE-ACSpa-cantlyreducedwithticagrelorcomparedwithclopidogrel[10.0%tients.157Cangrelor(30mg/kgbolusand4mg/kg/mininfusion)in-vs.12.3%;HR0.83(95%CI0.74,0.93),P¼0.0013]withsimilarre-itiatedatthecommencementofPCIhasbeenexaminedinthreeductionsforCVdeath[3.7%vs.4.9%;HR0.77(95%CI0.64,0.93),clinicaltrialsincludingatotalof24910patients:onewithclopidogrelP¼0.0070]andall-causemortality[4.3%vs.5.8%;HR0.76(95%CI(600mg)givenatthebeginningofPCI[CangrelorversusStandard0.64,0.90),P¼0.0020].154DifferencesinbleedingeventrateswereTherapytoAchieveOptimalManagementofPlateletInhibitionalsosimilarintheNSTE-ACSsubgroupcomparedwiththeoverall(CHAMPION)-PCI],onewithclopidogrel(600mg)initiatedatthestudy,withincreasedriskofnon-CABG-relatedPLATO-de nedendofPCI(CHAMPION-PLATFORM),andonewithclopidogrelmajorbleedswithticagrelorcomparedwithclopidogrel[4.8%vs.(300or600mg)initiatedeitherbeforeorafterPCIbasedonlocal3.8%;HR1.28(95%CI1.05,1.56),P¼0.0139]butnodifferenceclinicalpractice(CHAMPION-PHOENIX)amongpatientswithoutinlife-threateningorfatalbleeds.154Thebene tsofticagrelorcom-priorP2Y12orGPIIb/IIIainhibition.158–160Ameta-analysisoftheseparedwithclopidogrelinNSTE-ACSwereindependentofwhetherstudies,inwhich69%ofpatientswereundergoingPCIforACS,ob-ornotrevascularizationwasperformedinthe rst10daysafterran-serveda19%RRRinperiproceduraldeath,MI,ischaemia-drivenre-domization.154Thereductioninde nitestentthrombosiswithtica-vascularizationandstentthrombosis[cangrelor3.8%vs.clopidogrelgrelorintheNSTE-ACSsubgroup[1.1%vs.1.4%;HR0.71(95%CI4.7%;OR0.81(95%CI0.71,0.91),P¼0.007],witha39%RRRin0.43,1.17]wasconsistentwiththatseeninthetrialoverall[1.4%vs.stentthrombosisalone[cangrelor0.5%vs.clopidogrel0.8%;OR1.9%;HR0.67(95%CI0.50,0.90),P¼0.0091].155Inadditiontoin-0.61(95%CI0.43,0.80),P¼0.008].161ThecombinationofTIMIma-creasedratesofminorornon-CABG-relatedmajorbleedingeventsjorandminorbleedswasincreased[cangrelor0.9%vs.clopidogrelwithticagrelor,adverseeffectsincludeddyspnoea(without0.6%;OR1.38(95%CI1.03,1.86),P¼0.007],buttherewasnoin-bronchospasm),increasedfrequencyofasymptomaticventricularcreaseintherateoftransfusions.TheEuropeanCommissionissuedpausesandincreasesinuricacid.153,156

marketingauthorizationforthiscompoundinMarch2015.

Downloaded from http://www.77cn.com.cn/ by guest on August 30, 2015

2015ESC非ST段抬高心肌梗死治疗指南

ESCGuidelines

5.2.3TimingofP2Y12inhibitoradministration

InitiationofP2Y12inhibitorssoonafterthediagnosisofNSTE-ACSirrespectiveofmanagementstrategyhasbeenrecommended.162,163Thisimpliespretreatment,de nedasP2Y12inhibitoradministrationbeforecoronaryangiography,inpatientsscheduledforaninvasiveapproach.SubsequentlytheresultsoftheonlyRCTonP2Y12inhibi-torpretreatmentinNSTE-ACS,theComparisonofPrasugrelattheTimeofPercutaneousCoronaryInterventionorasPretreatmentattheTimeofDiagnosisinPatientswithNon-STElevationMyocardialInfarction(ACCOAST)trial,werepublished.164TheACCOASTstudycomparedpretreatmentwithprasugrel30mgandafurther30mgdosepriortoPCIwitharegimenofprasugrel60mgafterdiagnosticangiographybutpriortoPCIamong4033patientswithNSTEMIscheduledforearlyinvasivestrategy.Themediandurationofpretreatmentwas4.3h.Sixty-ninepercentofthepatientsunder-wentPCI,6%requiredsurgicalrevascularizationandtheremainderweretreatedconservatively.164At7days,patientsrandomizedtothepretreatmentarmexperiencednoreductionintheprimaryend-point(i.e.CVdeath,recurrentMI,stroke,urgentrevascularizationandbailoutuseofGPIIb/IIIainhibitors)[HR1.02(95%CI0.84,1.25),P¼0.81],andnobene tsemergedat30days.164TIMImajorbleedsweresigni cantlyincreasedinthepretreatmentgroupat7days[pretreatment2.6%vs.nopretreatment1.4%;HR1.90,(95%CI1.19,3.02),P¼0.006].Argumentsforandagainstpretreat-mentwithP2Y12inhibitorsinNSTE-ACSpatientshavebeendis-cussedextensivelyandthetopicremainscontroversial.165,166AstheoptimaltimingofticagrelororclopidogreladministrationinNSTE-ACSpatientsscheduledforaninvasivestrategyhasnotbeenadequatelyinvestigated,norecommendationfororagainstpretreat-mentwiththeseagentscanbeformulated.BasedontheACCOASTresults,pretreatmentwithprasugrelisnotrecommended.InNSTE-ACSpatientsplannedforconservativemanagement,P2Y12in-hibition(preferablywithticagrelor)isrecommended,intheabsenceofcontraindications,assoonasthediagnosisiscon rmed.5.2.4MonitoringofP2Y12inhibitors(seeWebaddenda)5.2.5Prematurediscontinuationoforalantiplatelettherapy

Withdrawaloforalantiplatelettherapymayleadtoanincreasedriskofrecurrentevents,particularlywhentherecommendedcourseoftherapyhasnotyetbeencompleted.176–178InterruptionofDAPTsoonafterstentimplantationincreasestheriskofstentthrombosis,especiallywithinthe rstmonthaftercessation.178Whilediscontinu-ationofDAPTpriortocardiacsurgeryisdiscussedinsection5.6.6.1Webaddendaand5.6.6.2,inthecaseofanon-cardiacsurgicalproced-urethatcannotbepostponed,aminimumof1and3monthsDAPTforbare-metalstents(BMSs)andnew-generationDESs,respectively,mightbeacceptable.179Inthissetting,surgeryshouldbeperformedinhospitalshavingcontinuouscatheterizationlaboratoryavailability,soastotreatpatientsimmediatelyincaseofperioperativeMI.179Ifinter-ruptionofDAPTbecomesmandatorybecauseofurgenthigh-risksurgery(e.g.neurosurgery)orinthecaseofamajorbleedthatcannotbecontrolledbylocaltreatment,noalternativetherapycanbepro-posedasasubstitutetoDAPTtopreventstentthrombosis.Lowmo-lecularweightheparin(LMWH)hasbeenadvocated,buttheproofofef cacyforthisindicationislacking.180Wheneverpossible,aspirinshouldbecontinuedbecauseearlydiscontinuationofbothantiplate-letdrugswillfurtherincreasetheriskofstentthrombosis.

Page19of59

Inpatientsundergoingelectivenon-cardiacsurgery,ticagrelorandclopidogrelshouldbediscontinued5daysbeforesurgery,whiletheintervalshouldbeincreasedto7daysinpatientsonprasugrel,unlessthepatientisathighriskofstentthrombosis.179Inthelattercase,amultidisciplinarydecisionisrequiredtodeterminethebeststrategy.Longerdiscontinuationtimes(e.g.7daysforticagrelorand10daysforclopidogrelorprasugrel)maybeappropriateforsurgeryatextremeriskofbleeding(e.g.sometypesofneurosur-gery).ForNSTE-ACSpatients,theriskofbleedsrelatedtosurgerymustbebalancedagainsttheriskofrecurrentischaemiceventsrelatedtodiscontinuationoftherapy.Thetypeofsurgery,theis-chaemicriskandextentofCAD,thetimesincetheacuteepisodeand,forpatientswhohaveundergonePCI,thetimesincethepro-cedureandthetypeofstentimplantedarekeyelementsofthedis-cussion.Selectedpatientswhorequirenon-cardiacsurgeryafterrecentlyimplantedstentsmaybene tfrombridgingtherapywithsmallmoleculeGPIIb/IIIainhibitors(i.e.tiro banorepti batide)afterdiscontinuationoftheP2Y12inhibitor,whilecangrelorhassofarbeentestedasbridgingtherapytoCABG.181,182InpatientsonDAPTfollowinganepisodeofNSTE-ACSthatwastreatedconser-vatively,theP2Y12inhibitormaybediscontinued.Insurgicalproce-dureswithlowtomoderatebleedingrisk,surgeonsshouldbeencouragedtooperateonpatientsonDAPT.AdherencetoDAPTshouldbeimprovedthrougheducationofpatients,relativesandphysiciansinordertopreventavoidableCVevents.

5.2.6Durationofdualantiplatelettherapy

InpatientswithNSTE-ACS,DAPTwithaspirinandclopidogrelhasbeenrecommendedfor1yearoveraspirinalone,irrespectiveofre-vascularizationstrategyandstenttype,accordingtotheClopidogrelinUnstableAnginatoPreventRecurrentEvents(CURE)study,whiletheTRITON-TIMI38andPLATOstudieshavedemonstratedthesuperiorityofaprasugrel-andticagrelor-basedregimen,re-spectively,overaclopidogrel-basedone.138,148,153A1-yeardurationofDAPTwithclopidogrelwasassociatedwitha26.9%RRRofdeath,MIorstroke(8.6%vs.11.8%;95%CI3.9,44.4;P¼0.02)vs.1-monthDAPTintheClopidogrelfortheReductionofEventsDuringObservation(CREDO)trial,whichenrolled2116pa-tients.183ThestudypopulationcomprisedpatientswithstableCADandlow-riskNSTE-ACSundergoingPCI(each50%),andnointeractionbetweenACSstatusandDAPTwasobserved.

EvidencetosupporttheextensionofDAPTafterDESbeyond1yearinNSTE-ACSpatientsislimited(Table9,seeWebaddenda).Table9(seeWebaddenda)Mainfeaturesofpublishedrandomizedstudiesinvestigatingvariousdurationsofdualantiplatelettherapyfollowingpercutaneouscoronaryintervention(PCI)

TheDAPTtrialrandomizedpatientswhodidnotexperiencead-verseeventsinthe rstyearafterPCItoanadditional18monthsofthienopyridine(clopidogrel/prasugrel)orplacebo.184Continuedtreatmentwiththienopyridine,ascomparedwithplacebo,reducedtheratesofstentthrombosis[0.4%vs.1.4%;HR0.29(95%CI0.17,0.48),P,0.001]andmajoradversecardiovascularandcerebrovas-cularevents[4.3%vs.5.9%;HR0.71(95%CI0.59,0.85),P,0.001].TherateofMIwaslowerwiththienopyridinetreatmentthanwithplacebo(2.1%vs.4.1%;HR0.47,P,0.001).Therateofdeathfromanycausewas2.0%inthegroupthatcontinuedthienopyridine

Downloaded from http://www.77cn.com.cn/ by guest on August 30, 2015

本文来源：https://www.bwwdw.com/article/309j.html