OfficialreprintfromUpToDate

www.uptodate.com2016UpToDate

OverviewoftheacutemanagementofSTelevationmyocardialinfarction
Authors
GuySReeder,MD
HaroldLKennedy,MD,MPH
RobertSRosenson,MD

SectionEditors
ChristopherPCannon,MD
JamesHoekstra,MD

DeputyEditor
GordonMSaperia,MD,FACC

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Feb2016.|Thistopiclastupdated:Jan14,2016.
INTRODUCTIONThefirststepinthemanagementofthepatientwithanacuteSTelevationmyocardial
infarction(STEMI)ispromptrecognition,sincethebeneficialeffectsoftherapywithreperfusionaregreatest
whenperformedsoonafterpresentation.Forpatientspresentingtotheemergencydepartmentwithchest
painsuspiciousforanacutecoronarysyndrome,thediagnosisofSTEMIcanbeconfirmedbythe
electrocardiogram.Biomarkersmaybenormalearly.(See"Criteriaforthediagnosisofacutemyocardial
infarction"and"Initialevaluationandmanagementofsuspectedacutecoronarysyndrome(myocardial
infarction,unstableangina)intheemergencydepartment".)
OncethediagnosisofanacuteSTEMIismade,theearlymanagementofthepatientinvolvesthe
simultaneousachievementofseveralgoals:
Reliefofischemicpain
Assessmentofthehemodynamicstateandcorrectionofabnormalitiesthatarepresent
Initiationofreperfusiontherapywithprimarypercutaneouscoronaryintervention(PCI)orfibrinolysis
Antithrombotictherapytopreventrethrombosisoracutestentthrombosis
Betablockertherapytopreventrecurrentischemiaandlifethreateningventriculararrhythmias
Thisisthenfollowedbytheinhospitalinitiationofdifferentdrugsthatmayimprovethelongtermprognosis:
Antiplatelettherapytoreducetheriskofrecurrentcoronaryarterythrombosisor,withPCI,coronary
arterystentthrombosis.
Angiotensinconvertingenzymeinhibitortherapytopreventremodelingoftheleftventricle
Statintherapy
Anticoagulationinthepresenceofleftventricularthrombusorchronicatrialfibrillationtoprevent
embolization
Thistopicwillsummarizeemergent/earlymanagementissuesforpatientswithacuteSTEMIandthendirect
thereadertoamoredetaileddiscussioninothertopics.Themanagementofthepatientafterareperfusion
strategyhasbeenchosenandcarriedoutisdiscussedseparately.(See"Overviewofthenonacute
managementofSTelevationmyocardialinfarction".)
ThemanagementofthepatientwithanonSTelevationMIorwithacomplicationofanacuteMI(eg,
cardiogenicshock,mitralregurgitation,ventricularseptaldefect)isdiscussedseparately.(See"Overviewof
theacutemanagementofunstableanginaandnonSTelevationmyocardialinfarction"and"Prognosisand
treatmentofcardiogenicshockcomplicatingacutemyocardialinfarction"and"Mechanicalcomplicationsof
acutemyocardialinfarction".)
STEMIAFTERNONCARDIACHOSPITALADMISSIONAminorityofpatientswhosustainanacuteST
elevationmyocardialinfarction(STEMI)dosowhilehospitalizedforanotherreason.Theapproachtosuch
patients,whichisdiscussedbelowinthistopic,isgenerallysimilartothatforpatientswhopresentto
emergencydepartments.However,patientswithSTEMIafterhospitaladmissionhavedifferentbaseline
characteristicsandhaveworseoutcomesthanthosewhopresenttotheemergencydepartment.

Threeobservationalstudieshighlightthesedifferences[13]:
Inpatientsareolderandmorelikelyfemale.Theyhavehigherratesofhypertension,chronickidney
disease,andpriorcerebrovascularevents,aswellasmorecomplexSTEMIpresentations(including
cardiacarrestandcardiogenicshock).
Thetimefromhealthcareproviderrecognitionoftheonsetoftheischemiceventtofirst
electrocardiogramissignificantlylongerininpatients.Thepercentofpatientswhoarewithin90
minutesislesswithSTEMIafterhospitaladmission(68versus91percent)[2].
CommonreasonsfortheinitialhospitaladmissioninpatientswithSTEMIafterhospitaladmission
includenonSTelevationacutecoronarysyndrome,surgery,respiratoryfailure,andpercutaneous
coronaryintervention(complicatedbystentthrombosis).
Coronaryangiographyandpercutaneouscoronaryinterventionareperformedinfewerindividualswith
inpatientSTEMI.
Inhospitalpatientshaveasignificantlyprolongedlengthofstayandarelesslikelytobedischarged
directlytohome.
TwoofthreestudiesfoundthatsurvivaltodischargeissignificantlylowerforinpatientSTEMI
(approximately65comparedto95percent),despitesimilarsizedinfarcts[1,3].Thethirdstudyfound
nodifference[2].
PatientswithSTEMIafterhospitaladmissionhaveahigheroneyearmortality(16.9versus9.4
percent)comparedtopatientswhopresentedtotheemergencydepartment[2].
GENERALPRINCIPLESThe2013AmericanCollegeofCardiologyFoundation/AmericanHeart
AssociationguidelineforthemanagementofacuteSTelevationmyocardialinfarction(STEMI)recommends
thateachcommunitydevelopandmaintainaregionalsystemofSTEMIcarethatencouragesassessment
andcontinuousqualityimprovementofemergencymedicalservicesandhospitalbasedSTEMIcare
activities[4,5].
Anincreasingnumberofcentersusestructuredalgorithms,checklists,orcriticalpathwaystoscreenpatients
withasuspectedacutecoronarysyndrome(ACS)[611].Thesestrategiescombinediagnosticevaluation
suchaselectrocardiographyandserumbiomarkerswiththerapeuticinterventionssuchasaspirin,beta
blockers,antithrombotictherapy,andprimarypercutaneouscoronaryintervention(PCI)orfibrinolytictherapy
(table1).(See"Initialevaluationandmanagementofsuspectedacutecoronarysyndrome(myocardial
infarction,unstableangina)intheemergencydepartment".)
ElderlypatientsAlthoughthemajorityofMIsintheelderlypopulationpresentwithelectrocardiograms
(ECGs)thatarenondiagnosticorhaveSTsegmentdepression,STEMIisnotuncommon[12].Itisestimated
that60to65percentofSTEMIsoccurinpatients65yearsofageand28to33percentoccurinpatients
75yearsofage[1214].Inaddition,asmanyas80percentofalldeathsrelatedtoMIoccurinpersons65
yearsofage.(See"OverviewoftheacutemanagementofunstableanginaandnonSTelevationmyocardial
infarction",sectionon'Elderlypatients'.)
Althoughpatientsage75andolderhavebeenunderrepresentedinclinicaltrialsofACS,thefollowing
observationsconcerningacuteMIinelderlycomparedtoyoungerpatientsaregenerallyaccepted[12]:
Elderlypatientsmorefrequentlyhaveanatypicalpresentation,includingsilentorunrecognizedMI
[12,15].Asanexample,chestpainispresentin57percentofpatients85yearsofagecomparedto
90percentforthoseunderage65.LeftbundlebranchblockandKillipclass2acuteheartfailureare
muchmorecommoninpatients85yearsofage(34and45percent,respectively).Delaysindiagnosis
havebeenwelldocumentedandoftenleadtodelaysintherapy.
Patients75yearsofagehaveahigherinhospitalmortality,whichoftenoccursinthosewithelectrical
andmechanicalcomplications[12].

 Outcomesinelderlypatients,asinyoungerpatients,appeartobebetterwithprimaryPCIthan
fibrinolysis[12].(See'Percutaneouscoronaryintervention'below.)
Elderlypatientsaremorelikelytohavefrequentandseverebleedingasaconsequenceof
antithrombotictherapy[12].Asanexample,theriskofstrokeasaconsequenceoffibrinolysisis
approximately2.9percentinpatients85yearsofage[12].Nevertheless,patients85yearsofage
whohavenocontraindicationstofibrinolysis,includingahighriskforintracranialhemorrhage,canbe
treatedwithfibrinolysis.(See'Fibrinolysis'belowand"FibrinolysisforacuteSTelevationmyocardial
infarction:Initiationoftherapy",sectionon'Stroke'.)
WomenTheapproachtowomenandmenshouldbethesame,despitethefactthatwomenhavemore
atypicalsymptoms,areolder,havegreaterdelaystopresentation,andhavehigherprevalenceof
hypertension.Inaddition,theyareathigherriskofbleeding.
MostwomenwhopresentwithanACSwillhaveacuteplaqueruptureasthecausehowever,coronary
arterydissectionmaybethecauseinyoungorperipartumindividuals.(See"Clinicalfeaturesanddiagnosis
ofcoronaryheartdiseaseinwomen",sectionon'Spontaneouscoronaryarterydissection'.)
Otherentitiessuchasmyocarditis,aorticdissection,orstressinducedcardiomyopathyshouldbe
considered.(See'MIwithnormalcoronaryarteries'belowand"Clinicalmanifestationsanddiagnosisof
myocarditisinadults",sectionon'Clinicalfeatures'and"Clinicalmanifestationsanddiagnosisofstress
(takotsubo)cardiomyopathy",sectionon'Clinicalmanifestations'and"Clinicalfeaturesanddiagnosisof
acuteaorticdissection",sectionon'Clinicalfeatures'.)
CocaineassociatedMIMIisawelldescribedcomplicationamongpatientspresentingwithcocaine
inducedischemicsymptoms.(See"Evaluationandmanagementofthecardiovascularcomplicationsof
cocaineabuse",sectionon'Myocardialinfarction'.)
Weagreewiththe2008AmericanHeartAssociationscientificstatementonthemanagementofcocaine
associatedchestpainandMI,whichstatesthatthesepatientsshouldbemanagedinamannersimilarto
otherACSpatients[16].Thefollowingtwopointswerealsomade:
Benzodiazepinesshouldbeadministeredearly
Betablockersshouldnotbeusedinthesettingofacutecocaineintoxicationwithchestpainduetothe
possibilityofexacerbationofcoronaryarteryvasoconstriction.
PossiblestentthrombosisTheinhospitalmortalityofSTEMIishigherinpatientswithcoronaryartery
stentthrombosisasthecause,asopposedtoarupturedplaque.ImmediatePCIisthetreatmentofchoice,
similartospontaneousMI.FibrinolysishasalsobeenusedforpatientswithSTEMIduetocoronaryartery
stentthrombosis.(See"Coronaryarterystentthrombosis:Incidenceandriskfactors"and"Longterm
antiplatelettherapyaftercoronaryarterystentinginstablepatients".)
INITIALASSESSMENTClinicalassessmentofthepatientwithapossibleacutecoronarysyndrome
(ACS)beginsassoonasthepatientarrivesintheemergencydepartmentandcontinuesinthecoronary
careunit.Initialassessmentconsistsofacutetriageandearlyriskstratification.Anelectrocardiogram(ECG)
shouldbeobtainedwithin10minutesofarrival,ifithasnotbeenobtainedalreadybyemergencymedical
serviceprovidersintheprehospitalarena.Adetailedapproachtotheevaluationandmanagementof
patientswithanACSintheemergencydepartmentisfoundseparately.
AcutetriageAfocusedevaluationonpresentationshouldaddress,inorderofimportance,thosefindings
thatpermitrapidtriageandinitialdiagnosisandmanagement:
Responsiveness,airway,breathing,andcirculationInpatientswhopresentwithrespiratoryor
cardiorespiratoryarrest,theappropriateresuscitationalgorithmsshouldbefollowed.(See"Advanced
cardiaclifesupport(ACLS)inadults"and"Supportivedataforadvancedcardiaclifesupportinadults
withsuddencardiacarrest"and"Basiclifesupport(BLS)inadults".)
Evidenceofsystemichypoperfusion(hypotensiontachycardiaimpairedcognitioncool,clammy,pale,
ashenskin)Cardiogenicshockcomplicatingacutemyocardialinfarction(MI)requiresaggressive

evaluationandmanagement.Thisissueisdiscussedindetailseparately.(See"Clinicalmanifestations
anddiagnosisofcardiogenicshockinacutemyocardialinfarction"and"Prognosisandtreatmentof
cardiogenicshockcomplicatingacutemyocardialinfarction".)
LeftheartfailurewithhypoxiaPatientswhopresentwithdyspnea,hypoxia,pulmonaryedema,and/or
impendingrespiratorycompromiserequireaggressiveoxygenation,airwaystabilization,diuretic
therapy,andafterloadreductioninadditiontothestandardtreatments.(See"Treatmentofacute
decompensatedheartfailure:Generalconsiderations".)
VentriculararrhythmiasSustainedventriculartachyarrhythmiasintheperiinfarctionperiodmustbe
treatedimmediatelybecauseoftheirdeleteriouseffectoncardiacoutput,possibleexacerbationof
myocardialischemia,andtheriskofdeteriorationintoventricularfibrillation.(See"Clinicalfeaturesand
treatmentofventriculararrhythmiasduringacutemyocardialinfarction"and'Arrhythmiapreventionand
management'below.)
EarlyriskstratificationAnalysesfromseverallargeclinicaltrialsandregistrieshaveestablisheda
numberofclinicalpredictorsofadverseoutcomesamongpatientswithacuteSTelevationMI(STEMI).
Therearemanyclinicalprognosticfactorsthatareimmediatelyavailabletothephysicianbaseduponthe
initialhistory,physicalexamination,ECG,andchestradiograph.Giventhespeedwithwhichreperfusion
therapyisadministeredinpatientswithSTEMI,theirclinicalutilityinearlymedicaldecisionmakinginthe
emergencydepartmentisoftenlimited.Theydoprovidegoodprognosticinformationthathasutilityinthe
postreperfusionperiod,however,andmayprovideguidanceregardingtheoptimummethodofreperfusion.
Highriskfeaturesincludeadvancedage,lowbloodpressure,tachycardia,heartfailure,andananteriorMI.
Specificscoringsystems,suchastheTIMIriskscore,permitafairlyprecisedeterminationoftheriskofin
hospitalmortality(calculator1)[17,18].
Patientsathighriskrequireanaggressivemanagementstrategyinadditiontostandardmedical
management.Directprehospitaltransportor,lessoptimally,promptinterhospitaltransfertoafacilitywith
revascularizationcapabilitiesisrecommendedforsuchpatients.
INITIALTHERAPYThepatientwithacuteSTelevationmyocardialinfarction(STEMI)shouldhave
continuouscardiacmonitoring,oxygen,andintravenousaccess.Therapyshouldbestartedtorelieve
ischemicpain,stabilizehemodynamicstatus,andreduceischemiawhilethepatientisbeingassessedasa
candidateforfibrinolysisorprimarypercutaneouscoronaryintervention(PCI).Otherroutinehospital
measuresincludeanxiolytics,serialelectrocardiograms,andbloodpressuremonitoring.Thefollowing
sectionssummarizeacutetherapy.
OxygenWerecommendsupplementaloxygentopatientswithanarterialsaturationlessthan90percent,
patientsinrespiratorydistress,includingthosewithheartfailure,orthosewithotherhighriskfeaturesfor
hypoxia.Untilbetterevidencetosupporttheuseofsupplementaloxygeninnormoxicpatientswithacute
MIisavailable,wesuggest(aweakrecommendation)notusingitinmostcases.
Supplementaloxygeninpatientswithouthypoxiamaybeofnovalueandperhapsharm.A2013Cochrane
reviewevaluatedfourtrialsof430patientswithpresumedMIwhowererandomlyassignedtosupplemental
oxygenorroomair[19].Thestudyfoundnosignificantdifferenceinmortality(pooledrelativerisk2.05,95%
confidenceinterval[CI]0.755.58inanintentiontotreatanalysisand2.11,95%CI0.785.68amongthose
withconfirmedMI).Nosubgroupanalysiswasperformedonthosewithnormoxia.
SubsequenttotheCochranereview,theAVOIDstudywaspublished[20].Inavoid,441normoxic(oxygen
saturation94percentonpulseoximeter)patientswithconfirmedSTEMIwererandomlyassigned,atthe
timeofelectrocardiographicdiagnosismadebyparamedics,toeitheroxygen(8L/min)ornosupplemental
oxygen.Thestudyshowednoimprovementintheprimaryendpointofadiminutionininfarctsizeas
measuredbycardiacenzymescTnIandcreatininekinase(CK)infact,therewasasignificantincreasein
meanpeakCKintheoxygengroup(1949versus1543U/Lmeansratio1.27,95%CI1.041.52).Atsix
months,theoxygengrouphadalargerMIsizeasmeasuredwithcardiacmagneticresonance.
Thesuggestionofharmwithsupplementaloxygenfoundinthesestudiesisofconcern,particularlyin

patientswithnormoxia,asapathophysiologicbasisforsuchharmhasbeenarticulated[21,22].Hyperoxia,
whichmightoccurwiththeadministrationofoxygentonormoxicindividuals,hasbeenshowntohavea
directvasoconstrictoreffectonthecoronaryarteries[21].
Thepotentialbenefitfromtheuseofhyperbaricoxygentherapywasevaluatedina2015metaanalysisof
sixsmallstudieswith665participantswithMIorsevereangina.Whileareductionintheriskofdeathwas
found(relativerisk0.58,95%CI0.360.92),methodologiclimitationsofthestudiespreventusfromhaving
confidenceintheuseofsuchtherapy[23].
ReperfusionPromptrestorationofmyocardialbloodflowisessentialtooptimizemyocardialsalvageand
toreducemortality(figure1)[24].Adecisionmustbemadeassoonaspossibleastowhetherreperfusion
willbeachievedwithfibrinolyticagentsorprimary(direct)PCI.(See"AcuteSTelevationmyocardial
infarction:Selectingareperfusionstrategy".)
PercutaneouscoronaryinterventionIfhighqualityPCIisavailable,multiplerandomizedtrialshave
shownenhancedsurvivalandalowerrateofintracranialhemorrhageandrecurrentMIcomparedto
fibrinolysis[25].Asaresult,2013AmericanCollegeofCardiologyFoundation/AmericanHeartAssociation
guidelineforthemanagementofSTEMIrecommendsuseofprimaryPCIforanypatientwithanacute
STEMIwhocanundergotheprocedureinatimelymannerbypersonsskilledintheprocedure[4,5].Timely
isdefinedasanidealfirstmedicalcontacttoPCItimeof90minutesorlessforpatientstransportedtoPCI
capablehospitalor120minutesorlessforpatientswhoinitiallyarriveatoraretransportedtoanonPCI
capablehospitalandarethentakentoaPCIcapablehospital.
Patientswithtypicalandpersistentsymptomsinthepresenceofaneworpresumablynewleftbundle
branchblockarealsoconsideredeligible.(See"PrimarypercutaneouscoronaryinterventioninacuteST
elevationmyocardialinfarction:Determinantsofoutcome".)
Forpatientspresenting12to24hoursaftersymptomonset,theperformanceofprimaryPCIisreasonableif
thepatienthassevereheartfailure,hemodynamicorelectricalinstability,orpersistentischemicsymptoms.
RandomizedtrialsofroutinelatePCIhaveshownanimprovementinleftventricularfunctionbutnotinhard
clinicalendpoints.Thisapproachisnotrecommended.(See"Coronaryarterypatencyandoutcomeafter
myocardialinfarction",sectionon'LatePCItoopenanoccludedartery'.)
IfprimaryPCIisnotavailableonsite,rapidtransfertoaPCIcentercanproducebetteroutcomesthan
fibrinolysis,aslongasthedoortoballoontime,includinginterhospitaltransporttime,islessthan90
minutes.Thisdoortoballoontimeisdifficulttoobtainunlessrapidtransportprotocolsandrelativelyshort
transportdistancesareinplace.(See"PrimarypercutaneouscoronaryinterventioninacuteSTelevation
myocardialinfarction:Determinantsofoutcome".)
WesuggestthefollowingapproachforpatientswithSTEMIathospitalswithoutonsitePCIcapability:
Forpatientswhopresentwithintwohoursoftheonsetofsymptoms,wesuggestfulldoselytictherapy
andtransfertoaPCIcenter.ThisassumesthatprimaryPCIcannotbeperformedinlessthan90
minutesatalocalPCIcenter.
Forpatientswhopresentwithsymptomsgreaterthantwotothreehours,wesuggesttransferfor
primaryPCI.However,therearetimeswhenthepatientpresentsaftertwohoursandPCIcannotbe
accomplishedinlessthan120minutes.Inthissetting,clinicaljudgementneedstobeexercised
fibrinolytictherapymaybeappropriateinpatientswithupto12hoursofsymptoms.
Asnotedabove,allpatientswhoundergoprimaryPCIshouldbepretreatedatdiagnosiswithanticoagulant
andantiplatelettherapy.(See'Antiplatelettherapy'belowand'Anticoagulanttherapy'below.)
FibrinolysisThe2013AmericanCollegeofCardiologyFoundation/AmericanHeartAssociation
guidelineforthemanagementofSTEMIrecommendstheuseoffibrinolytictherapyinpatientswithsymptom
onsetwithin12hourswhocannotreceiveprimarypercutaneouscoronaryinterventionwithin120minutesof
firstmedicalcontact(table2AB)[4,5].Thetimeintervalfromhospitalarrivaltoinitiationoffibrinolyticdrug
infusionshouldbelessthan30minutes[4,5,26,27].(See"AcuteSTelevationmyocardialinfarction:
Selectingareperfusionstrategy"and"FibrinolysisforacuteSTelevationmyocardialinfarction:Initiationof

therapy",sectionon'Timing'.)
Fibrinolytictherapyhasgenerallynotimprovedoutcomesinpatientspresentingat12hoursorlaterandis
thereforenotindicatedinthosewhoarestableandasymptomatic.However,fibrinolysiscanbeconsidered
upto24hoursaftersymptomonsetifthepatienthasongoingorstutteringchestpainandPCIisnot
available.(See"FibrinolysisforacuteSTelevationmyocardialinfarction:Initiationoftherapy",sectionon
'Timing'.)
Anumberofdifferentfibrinolyticregimenshavebeenevaluatedandeachagenthasitsownpreferreddosing
regimen(table3).(See"Characteristicsoffibrinolytic(thrombolytic)agentsandclinicaltrialsinacuteST
elevationmyocardialinfarction".)
Patientsreceivingfibrinolytictherapybenefitfrompretreatmentwithclopidogrelbutnotaglycoprotein(GP)
IIb/IIIainhibitor[27].(See"AntiplateletagentsinacuteSTelevationmyocardialinfarction".)
AngiographyafterfibrinolysisFibrinolysisimmediatelybeforeprimaryPCI,previouslycalled
facilitatedPCI,isnotrecommended.(See"PercutaneouscoronaryinterventionafterfibrinolysisforacuteST
elevationmyocardialinfarction",sectionon'FacilitatedPCI'.)
Thedataevaluatingtheroleofelectivecoronaryangiography,whichmightincludeadjunctiveandearly
electivePCI,arediscussedindetailelsewhere.(See"AcuteSTelevationmyocardialinfarction:Selectinga
reperfusionstrategy",sectionon'FibrinolysisfollowedbyPCI'.)
Theuseof"rescuePCI"forpatientswithrecurrentischemiaorinfarctionisbetterestablished.(See
"Managementoffailedfibrinolysis(thrombolysis)orthreatenedreocclusioninacuteSTelevationmyocardial
infarction",sectionon'Primaryfailure'.)
BypasssurgeryCoronaryarterybypassgraftsurgery(CABG)isinfrequentlyperformedinpatients
withSTEMI.ThemainindicationsareforemergentorurgentCABGrelatedtofailureoffibrinolysisorPCI,or
hemodynamicallyimportantmechanicalcomplications.(See"Coronaryarterybypassgraftsurgeryafter
acuteSTelevationmyocardialinfarction".)
ThebenefitofrevascularizationmustbeweighedagainsttheincreaseinmortalityassociatedwithCABGin
thefirstthreetosevendaysafterSTEMI.Thus,ifthepatienthasstabilized,surgeryshouldbedelayedto
allowmyocardialrecovery.PatientswithcriticalanatomyshouldundergoCABGduringtheinitial
hospitalization.
MedicationsAsummaryofthespecificagentslistedbelowandtheirusualdosingregimensisfound
elsewhere.(See"Initialevaluationandmanagementofsuspectedacutecoronarysyndrome(myocardial
infarction,unstableangina)intheemergencydepartment",sectionon'STelevation'.)
AntiplatelettherapyAntiplatelettherapyincludingaspirin,aP2Y12receptorblocker,and,inpatients
undergoingprimaryPCI,aGPIIb/IIIainhibitorimprovesoutcomes.Theseagentsarediscussedindetail
elsewhere.(See"AntiplateletagentsinacuteSTelevationmyocardialinfarction".)
AnticoagulanttherapyTheevidencetosupportparenteralanticoagulanttherapyinmostcasesof
STEMIisstrong.However,theevidencetorecommendoneagentoveranotherislessrobust,inpart
becauseitisderivedfrommanystudiesthatwereperformedbeforethecurrenteraofaggressiveantiplatelet
therapyorstudiesthatconflictwitheachother.Thechoiceofagentdependsupontheoveralltreatment
strategydesignedforeachpatient:fibrinolytictherapywitheitherfibrinspecificornonfibrinspecificagents,
primaryPCI,ornoreperfusion.(See"AnticoagulanttherapyinacuteSTelevationmyocardialinfarction".)
NitratesIntravenousnitroglycerinisusefulinpatientswithpersistentchestpainafterthreesublingual
nitroglycerintablets,aswellasinpatientswithhypertensionorheartfailure.(See"Nitratesinthe
managementofacutecoronarysyndrome".)
However,nitratesmustbeusedwithcautionoravoidedinsettingsinwhichhypotensionislikelyorcould
resultinserioushemodynamicdecompensation,suchasrightventricularinfarctionorsevereaorticstenosis.
Inaddition,nitratesarecontraindicatedinpatientswhohavetakenaphosphodiesteraseinhibitorforerectile
dysfunction(orpulmonaryhypertension)withintheprevious24hours.(See"Sexualactivityinpatientswith

cardiovasculardisease"and"Rightventricularmyocardialinfarction",sectionon'Optimizationofright
ventricularpreload'.)
MorphineMorphinemaybegivenforthereliefofchestpaininthesettingofacutemyocardial
infarction.Wegenerallyreserveitsuseforpatientswithanunacceptablelevelofpain,duetoevidenceof
worseoutcomesinpatientsreceivingthedrug.Wegiveintravenousmorphinesulfateataninitialdoseof2
to4mg,withincrementsof2to8mgrepeatedat5to15minuteintervals.
Inastudyof57,039patientsenrolledintheCRUSADEInitiative,anonrandomized,retrospective
observationalregistryofpatientswithnonSTelevationacutecoronarysyndrome,thosetreatedwith
morphine(29.8percent)hadahigheradjustedriskofdeaththanthosenot(oddsratio1.48,95%CI1.33
1.64)[28].
Whilethemechanism(s)bywhichmorphinemightbeassociatedwithdecreasedsurvivalisnotknown,at
leasttwostudieshaveraisedthepossibilitythatitactsbyinterferingwiththeantiplateleteffectoftheP2Y12
receptorblockers(see"AntiplateletagentsinacuteSTelevationmyocardialinfarction",sectionon'Choosing
antiplatelettherapy'):
IntheIMPRESSIONtrial,70acuteMIpatientstreatedwithticagrelorwererandomlyassignedto
receiveintravenousmorphine(5mg)orplacebo[29].Morphinelowered(active)ticagrelorplasma
concentrationandimpaireditsantiplateleteffect.
Inastudyof24healthysubjectswhoreceivedaloadingdoseof600mgofclopidogrelandeither5mg
ofintravenousmorphineorplacebo,morphinesignificantlydelayedclopidogrelresorptionandreduced
theareaunderthecurvelevelsofitsactivemetaboliteby52percent[30].Plateletinhibition,as
measuredbymultipletests,waslesspronouncedinthosegivenmorphine.
Inastudyof50patientswithSTEMIundergoingprimaryPCIwhowererandomlyassignedtoeither
prasugrelorticagrelor,morphinewasanindependentpredictorofhighresidualplateletreactivityattwo
hours(oddsratio5.29,95%CI1.4419.49)[31].
BetablockersOralbetablockersareadministereduniversallytoallpatientswithoutcontraindications
whoexperienceanacuteSTEMI[4,5].Contraindicationsincludeheartfailure,evidenceofalowoutputstate,
highriskforcardiogenicshock,bradycardia,heartblock,orreactiveairwaydisease.(See"Acutemyocardial
infarction:Roleofbetablockertherapy".)
StatintherapyIntensivestatintherapyshouldbeinitiatedasearlyaspossibleinallpatientswith
STEMI[32,33].
UpToDaterecommendstherapywithatorvastatin80mg/day,whichwasusedinthePROVEITTIMI22and
MIRACLtrials.Amongpatientswhowerepreviouslytreatedwithadifferentstatinregimen,UpToDate
suggestsswitchingtoatorvastatin80mg/day.(See"Lowdensitylipoproteincholesterol(LDLC)lowering
afteranacutecoronarysyndrome",sectionon'Continuationofpriorstatintherapy'.)
Initialintensivestatintherapy,ratherthangradualdosetitrationupward,isrecommendedbecauseofthe
suggestionofbenefitinthePROVEITTIMI22trialwithin30days[32].(See"Lowdensitylipoprotein
cholesterol(LDLC)loweringafteranacutecoronarysyndrome".)
Basedontheserecommendations,mostpatientsshouldhavealipidprofileperformedearlyintheir
hospitalization,althoughsomepatientsmayhavehadrecentoutpatienttesting.Intheeventthattestingis
notperformedearlyafteranacutecoronarysyndrome,valuesobtaineduptofourdaysaftertheeventmay
representbaselinevalues.(See"Measurementofbloodlipidsandlipoproteins",sectionon'AfteranACS'.)
Evaluationoftheresponsetostatintherapyafteranacutecoronarysyndromeshouldbedeferredfortwo
months,sinceacutephaseresponsesandperhapsotherfactorscantransientlylowerlowdensitylipoprotein
(LDL)cholesterolby40to50percentandthus,insomepatients,causespuriouslynormalappearinglevels
followinganacutecoronarysyndrome.However,themagnitudeofthiseffect,atleastsoonafter
hospitalization,appearstobelesswithcurrenttherapiesthatlimitthedegreeofmyocardialinjury,suchas
PCIorfibrinolytictherapy[34].(See"Lowdensitylipoproteincholesterol(LDLC)loweringafteranacute

coronarysyndrome"and"Measurementofbloodlipidsandlipoproteins",sectionon'AfteranACS'.)
ThelongtermLDLcholesterolgoalisdiscussedseparately.(See"Intensityoflipidloweringtherapyin
secondarypreventionofcardiovasculardisease".)
Other
ArrhythmiapreventionandmanagementBothatrialandventriculararrhythmiascanbeseenduring
andaftertheacutephaseofSTEMI.Theseincludeatrialfibrillationorflutter,whichcancausesymptomatic
hypoperfusionduetoarapidrate,andlifethreateningventriculartachycardiaorventricularfibrillation.(See
"Supraventriculararrhythmiasaftermyocardialinfarction"and"Clinicalfeaturesandtreatmentofventricular
arrhythmiasduringacutemyocardialinfarction".)
Prophylacticintravenousorintramuscularlidocainetopreventventriculartachycardia/ventricularfibrillationin
theacuteMIpatientisNOTrecommended[35].Recommendedprophylacticmeasuresincludeearly
administrationofanintravenousbetablockerandtreatmentofhypokalemiaandhypomagnesemia.
TreatmentofventriculartachyarrhythmiasinthesettingofacuteMIisdiscussedseparately.(See"Clinical
featuresandtreatmentofventriculararrhythmiasduringacutemyocardialinfarction".)
SinusbradycardiacanoccurinpatientswithSTEMI,especiallywhentheinferiorwallisinvolved.Ifthe
patientissymptomatic,therapywithatropineisindicated.Persistentsinusbradycardiamayrequire
temporarypacing.(See"Supraventriculararrhythmiasaftermyocardialinfarction",sectionon'Sinus
bradycardia'.)
AtrioventricularnodalandintraventricularconductionabnormalitiesalsomaybeseeninSTEMI,particularly
oftheanteriorwall.Ifthepatientissymptomatic,temporarypacingisindicated.Asymptomaticpatientswith
certaintypesofconductionabnormalitiesmayalsorequireprophylactictemporarypacemakertherapy,and
somemayrequirepermanentpacemakerimplantation.(See"Conductionabnormalitiesaftermyocardial
infarction".)
NonsteroidalantiinflammatorydrugsNonsteroidalantiinflammatorydrugs(exceptaspirin)should
bediscontinuedimmediatelyduetoanincreasedriskofcardiovasculareventsassociatedwiththeiruse.
(See"NonselectiveNSAIDs:Adversecardiovasculareffects".)
PotassiumandmagnesiumAlthoughtherearenoclinicaltrialsdocumentingthebenefitsof
electrolytereplacementinacuteMI,theAmericanCollegeofCardiology/AmericanHeartAssociation
guidelinesrecommendmaintainingtheserumpotassiumconcentrationabove4.0meq/Landaserum
magnesiumconcentrationabove2.0meq/L(2.4mg/dLor1mmol/L)[36].Muchoftheevidenceforthis
recommendationwasderivedfromstudiesbeforetheroutineuseofbetablockerandtheuseofreperfusion
inmanypatients.(See"Clinicalfeaturesandtreatmentofventriculararrhythmiasduringacutemyocardial
infarction",sectionon'Ventricularfibrillation'.)
A2012retrospectivecohortstudyofalmost39,000individualsfoundthatforpatientswithacuteMI,the
lowestmortalitywasobservedinthosewithpostadmissionserumpotassiumvaluesbetween3.5and<4.5
meq/L[37].(See"RiskfactorsforadverseoutcomesafterSTelevationmyocardialinfarction",sectionon
'Serumpotassium'.)
Wesuggestthattheserumpotassiumfallwithintherangeof3.5to4.5meq/L.Itmaybedifficulttolowerthe
potassiumbelow4.5meq/Linsomepatients,suchasthosewithchronickidneydisease.
ErythropoietinClinicalinterestintheuseoferythropoietinasacardioprotectiveagentemanatedfrom
agrowingbodyofexperimentalevidenceshowingthaterythropoietinsnonerythropoieticeffectsinclude
antiinflammatory,antiapoptotic,andangiogenicproperties.Preclinicalstudiessuggestedthaterythropoietin
maybecardioprotectiveinpatientswithacuteSTEMI,basedonimprovementininfarctsizeattributedtoits
antiapoptoticandangiogenicproperties.However,intheREVEALtrial,whichrandomlyassigned222
patientswhounderwentsuccessfulPCItoeitherintravenouserythropoietinorplacebowithinfourhoursof
theprocedure,therewasnosignificantdifferencebetweenthegroupsininfarctsize,expressedas
percentageofleftventricularmassasassessedbycardiacmagneticresonanceimagingperformedat
baselineandat10to14weeks[38].Inaddition,asignificantlyincreasedriskofdeath,recurrentMI,stroke,

orstentthrombosisinerythropoietintreatedpatientssuggestedanincreasedthromboticriskdueto
erythropoietininpatientswithSTEMI.Thisobservationofadverseeventshasbeennotedinotherstudiesof
noncardiacpopulations[3941].
IntravenousglucoseinsulinpotassiumBasedontheavailableevidence,wedonotrecommend
theuseofintravenousglucoseinsulinpotassium(GIK)toimproveoutcomesinpatientswithsuspectedor
diagnosedacuteMI.Reviewsofthepotentialmechanismofactionandpotentialbenefitshavebeen
published[42].
Experimentalandearlyclinicalevidencesuggestedthatmetabolicsupportoftheischemicmyocardiummay
limittheextentofmyocardialinjuryanddecreasethefrequencyofpotentiallylethalarrhythmiasafterMI.GIK
wasthoughttobeapossibleapproachtoimprovingmyocardialenergymetabolism[43].A1997meta
analysisofearlytrialsofGIKfoundasignificantreductionininhospitalmortality[44].
Moretrials,inwhichpatientsreceivedcurrenttherapiesforacutecoronarysyndromessuchasurgentPCI,
aggressiveantithrombotictherapy,andastatindrug,havenotprovidedconclusiveevidenceofbenefit[45
50].TheCREATEECLAandIMMEDIATEtrialsprovidethebestevidenceagainstabenefitfromGIK:
TheCREATEECLAtrialevaluated20,201patientswithanacuteSTEMIwhopresentedwithin12
hoursofsymptomonset[45].ThepatientswererandomlyassignedtoaGIKinfusionorplacebofor24
hours.Reperfusionwasperformedin83percentofpatients(74percentwiththrombolytictherapyand
9percentwithprimaryPCI).TheGIKinfusionwasbegunatthetimeofrandomization.
At30days,therewasnodifferencebetweenthetwogroupsinmortality(10versus9.7percentwith
usualcare),cardiacarrest(1.5versus1.4percent),cardiogenicshock(6.3versus6.6percent),or
reinfarction(2.4versus2.3percent).ApotentiallimitationofthistrialwastherelativelylateuseofGIK:
Themediantimefromsymptomonsettotreatmentwasapproximatelysixhours.
TheIMMEDIATEtrialrandomlyassigned871patientswithsuspectedacutecoronarysyndromes
(approximately40percentwithSTelevationonthepresentingelectrocardiogram)tointravenousGIK
oridenticalappearing5percentglucoseplacebo,whichwasadministeredbyparamedicsintheoutof
hospitalsettingandcontinuedfor12hours[46].Therewasnodifferenceintherateofprogressionto
MI(asmeasuredbybiomarkersandECGevidence)at24hoursortherateofdeathat30daysamong
patientswhoreceivedGIKcomparedtothosewhoreceivedplacebo(48.7versus52.6percentodds
ratio0.88,95%CI0.661.13and4.4versus6.1percentoddsratio0.72,95%CI0.401.29,
respectively).
MIWITHNORMALCORONARYARTERIESAtthetimeofcoronaryangiography,asmanyas7percent
ofpatientswithacuteSTelevationmyocardialinfarction(MI)donothaveacriticalcoronaryarterylesion
[51],includingapproximately3percentwhohavenormalepicardialcoronaryarteries[5254].The
prevalenceisgreaterinyoungerpatientsandinwomen[51].Potentialmechanismsthatcanbeidentifiedin
someofthesepatientsincludecoronaryspasm,acquiredorinheritedcoagulationdisorders,toxinssuchas
cocaine,collagenvasculardisease,embolism,myocarditis,andmicrovasculardisease[53].Theprevalence
oflackofacriticallesionornormalepicardialcoronaryarteriesmayalsobehigherinreferralpopulations,
dueinparttomisinterpretationofthepresentingelectrocardiogram(respectivevalues14and9.5percent,
respectively,inareviewof1335referredpatients)[55].(See"Coronaryheartdiseaseandmyocardial
infarctioninyoungmenandwomen"and"Vasospasticangina"and"Evaluationandmanagementofthe
cardiovascularcomplicationsofcocaineabuse"and"Clinicalmanifestationsanddiagnosisofmyocarditisin
adults",sectionon'Electrocardiogram'and"CardiacsyndromeX:Anginapectoriswithnormalcoronary
arteries",sectionon'Clinicalfeatures'.)
Stressinducedcardiomyopathy(takotsubocardiomyopathy)isanincreasinglyreportedsyndrome,generally
characterizedbytransientsystolicdysfunctionoftheapicaland/ormidsegmentsoftheleftventriclethat
mimicsMI,butintheabsenceofsignificantcoronaryarterydisease.Thisissueisdiscussedelsewhere.
(See"Clinicalmanifestationsanddiagnosisofstress(takotsubo)cardiomyopathy".)
Inastudyof323women45yearsorolderwhopresentedtoacommunityhospitaloveroneyearandwho
werediagnosedwithanacuteMI(includinganelevatedtroponin),5.9percentmetcriteriaforstressinduced

cardiomyopathy[56].
SUMMARYAcuteSTelevationmyocardialinfarction(STEMI)isamedicalemergencyrequiringthe
simultaneousapplicationofmultipletherapies.Aftertheemergentperiod,othertherapiesmayneedtobe
started.(See"OverviewofthenonacutemanagementofSTelevationmyocardialinfarction".)
Womenshouldbemanagedsimilarlytomen.OtherpatientswithacuteSTEMI,suchastheelderlyand
thosewitheithercocaineassociatedMIorpossiblestentthrombosis,aremanagedsomewhatdifferently.
(See'Generalprinciples'above.)
TheinitialassessmentandtherapyofSTEMIissummarizedintableform(table1).
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
Topic66Version47.0

GRAPHICS
Rapidoverview:Managementofacutecoronarysyndrome(ACS)
Initialassessment:
Considerthediagnosisinpatientswithchestdiscomfort,shortnessofbreath,orother
suggestivesymptoms.Women,olderadults,andpatientswithdiabetesmayhave
"atypical"presentations.
Obtain12leadECGwithin10minutesofarrivalrepeatevery10to15minutesifinitial
ECGisnondiagnosticbutclinicalsuspicionremainshigh(initialECGoftenNOT
diagnostic).
1.STEMI:STsegmentelevations1mm(0.1mV)intwoanatomicallycontiguous
leadsor2mm(0.2mV)inleadsV2andV3ORnewleftbundlebranchblockand
presentationconsistentwithACS.IfECGsuspiciousbutnotdiagnostic,consult
cardiologistearly.
2.NonSTEMIorunstableangina:STsegmentdepressionsordeepTwaveinversions
withoutQwavesorpossiblynoECGchanges.
ObtainemergentcardiologyconsultationforACSpatientswithcardiogenicshock,left
heartfailure,orsustainedventriculartachyarrhythmia.

Initialinterventions:
Assessandstabilizeairway,breathing,andcirculation.
Attachcardiacandoxygensaturationmonitorsprovidesupplementaloxygenasneeded
tomaintainO 2 saturation>90%.EstablishIVaccess.
TreatsustainedventriculararrhythmiarapidlyaccordingtoACLSprotocols.
Giveaspirin325mg(nonentericcoated)tobechewedandswallowed(unlessaortic
dissectionisbeingconsidered).Iforaladministrationisnotfeasible,giveasrectal
suppository.
Performfocusedhistoryandexamination:Lookforsignsofhemodynamiccompromise
andleftheartfailuredeterminebaselineneurologicfunction,particularlyiffibrinolytic
therapyistobegiven.
Obtainbloodforcardiacbiomarkers(troponinpreferred),electrolytes,
hematocrit/hemoglobin.Performcoagulationstudiesforpatientstakinganticoagulants
orasotherwiseindicated(eg,knowncoagulopathy).
Givethreesublingualnitroglycerintablets(0.4mg)oneatatime,spacedfiveminutes
apart,oroneaerosolsprayundertongueeveryfiveminutesforthreedosesIFpatient
haspersistentchestdiscomfort,hypertension,orsignsofheartfailureANDthereisno
signofhemodynamiccompromise(eg,rightventricularinfarction)andnouseof
phosphodiesteraseinhibitors(eg,forerectiledysfunction)addIVnitroglycerinfor
persistentsymptoms.
Treatleftheartfailureifpresent:Giveafterloadreducingagent(eg,nitroglycerin
sublingualtabletand/orIVdripat40mcg/minuteprovidednohypotensionandno
phosphodiesteraseinhibitors[eg,forerectiledysfunction]titratedripupquicklybased
onresponse)giveloopdiuretic(eg,intravenousfurosemide)administernoninvasive
positivepressureventilation(eg,BLPAP)toappropriatepatients.

Givebetablocker(eg,metoprololtartrate25mgorally)IFnosignsofheartfailureand
notathighriskforheartfailureandnosignsofhemodynamiccompromise,bradycardia,
orseverereactiveairwaydisease.Ifhypertensive,mayinitiatebetablockerIVinstead
(eg,metoprololtartrate5mgintravenouseveryfiveminutesforthreedosesas
tolerated).
Givemorphinesulfate(2to4mgslowIVpushevery5to15minutes)forunacceptable,
persistentdiscomfortoranxietyrelatedtomyocardialischemia.
Start80mgofatorvastatinasearlyaspossibleandpreferablybeforePCIinpatients
notonstatin.Ifpatientistakingalowtomoderateintensitystatin,switchto
atorvastatin80mg.

AcutemanagementSTEMI:
Selectreperfusionstrategy:PrimaryPCIstronglypreferred,especiallyforpatientswith
cardiogenicshock,heartfailure,latepresentation,orcontraindicationstofibrinolysis.
Activatecardiaccatheterizationteamasindicated.Forpatientswithsymptomsof>12
hours,fibrinolytictherapyisnotindicated,butemergentPCImaybeconsidered,
particularlyforpatientswithevidenceofongoingischemiaorthoseathighriskofdeath.
TreatwithfibrinolysisifPCIunavailablewithin120minutesoffirstmedicalcontact,
symptoms<12hours,andnocontraindications.*
Giveoralantiplatelettherapy(inadditiontoaspirin)toallpatients:
1.Patientstreatedwithfibrinolytictherapy:Giveclopidogrelloadingdose300
mgifage75yearsorlessifageover75years,giveloadingdoseof75mg.
2.Patientstreatedwithnoreperfusiontherapy:Giveticagrelorloadingdose
180mg.
3.PatientstreatedwithprimaryPCI:Giveticagrelorloadingdoseof180mgor
prasugrelloadingdoseof60mg(ifnocontraindications:priorstrokeorTIA,or
relativecontraindicationsforprasugrelsuchasthoseage75yearsorolder,weight
lessthan60kg).Forpatientsathighriskofbleedingorthoseforwhomprasugrelor
ticagrelorcannotbeused,wegiveclopidogrel600mg.
Giveanticoagulanttherapytoallpatients:
1.ForpatientstreatedwithprimaryPCI,wepreferUFHtobivalirudin.This
recommendationassumesthatpatientswillreceiveapotentoralantiplateletagent
(ticagrelororprasugrel),whichweprefertoclopidogrel.Forthosepatientswho
receiveclopidogrel,wepreferbivalirudin.
DosingofUFH:AninitialIVbolusof50to70units/kguptoamaximumof
5000units.Additionalheparinmaybegiveninthecatheterizationlaboratory
basedontheresultsofACTmonitoring.
Dosingofbivalirudin:Initialbolusof0.75mg/kgIVfollowedbyIVinfusion
of1.75mg/kgperhourcanbediscontinuedafterPCI.
2.Forpatientstreatedwithfibrinolysis,wepreferenoxaparinforpatientsnotat
highbleedingriskorfondaparinuxforthoseathighbleedingrisk.Forthosepatients
inwhomPCIispossibleorlikelyafterfibrinolytictherapy,UFHisreasonable.
Dosingofenoxaparin
Patients<75years:Loadingdoseof30mgIVbolusfollowedby1mg/kg
subcutaneouslyevery12hoursmaximumof100mgforthefirsttwo
subcutaneousdoses.Thefirstsubcutaneousdoseshouldbeadministered
withtheIVbolus.

Doseadjustmentforrenalimpairment(Crcl<30mL/minute)*:Loading
doseof30mgIVfollowedby1mg/kgsubcutaneouslyevery24hours.
ThefirstsubcutaneousdoseshouldbeadministeredwiththeIVbolus.
Patients75years:NoIVloadingdose.Administer0.75mg/kg
subcutaneouslyevery12hoursmaximumof75mgforthefirsttwodoses.
Doseadjustmentforrenalimpairment(Crcl<30mL/minute)*:NoIV
loadingdose.Administer1mg/kgsubcutaneouslyevery24hours.
SupplementalIVbolusdoseforpatientswhowillreceivePCIafter>1dose
oftherapeuticenoxaparin:0.3mg/kgiflastenoxaparindosewasgiven8to
12hoursearliernosupplementalIVdoseiflastenoxaparindosewas
within8hoursuseUFHiflastenoxaparindosewasmorethan12hours
ago.
DosingofUFH:IVbolusof60to100units/kgtoamaximumof4000units,
followedbyanIVinfusionof12units/kgperhour(maximum1000unitsper
hour)adjustedtoachieveagoalaPTTofapproximately50to70seconds(1.5
to2timescontrol).
Dosingoffondaparinux:2.5mgintravenously,followedby2.5mg
subcutaneouslyevery24hours.Thisdrugshouldbeavoidedincreatinine
clearance<30mL/minute.
3.Forpatientsnotreceivingreperfusiontherapy,weuseenoxaparinorUFH.
Dosingofenoxaparin:Dosesameasforpatientstreatedwithfibrinolysis
(refertosection2above).
DosingofUFH:IVbolusof50to70units/kgtoamaximumof5000units,
followedbyanIVinfusionof12units/kgperhouradjustedtoachieveagoal
aPTTofapproximately50to70seconds(1.5to2timescontrol).

AcutemanagementofunstableanginaornonSTEMI:
Giveantiplatelettherapy(inadditiontoaspirin)toallpatients:
1.Patientsnottreatedwithaninvasiveapproach:Giveticagrelorloadingdose
180mg.Forthesepatientswhoareatveryhighrisk(eg,recurrentischemic
discomfort,dynamicECGchanges,orhemodynamicinstability),consideraddingaGP
IIb/IIIainhibitor(eithereptifibatideortirofiban).
2.Forpatientsmanagedwithaninvasiveapproach:Giveticagrelorloading
doseof180mgatpresentation.Prasugrelloadingdoseof60mgmaybeusedasan
alternativeifgivenafterdiagnosticcoronaryangiography.
Forpatientsage75yearsorolder,weightlessthan60kg,orpaststrokeor
transientischemicattack,ticagrelororclopidogrelarepreferredtoprasugrel.
Clopidogrelmaybegiveninadoseof300to600mg,butweprefer600mg.For
patientsotherwiseathighriskforbleedingduetopriorhemorrhagicstroke,
ongoingbleeding,bleedingdiathesis,orclinicallyrelevantanemiaor
thrombocytopenia,clopidogrel300to600mgisanoption.
Forpatientstreatedwithaninvasiveapproachandwhoreceivebivalirudin,wedo
notrecommendroutinelygivingaGPIIb/IIIainhibitorforthosepatientstreated
withheparinandwhoaretroponinpositive,wesuggestaddingaGPIIb/IIIa
inhibitor(eitherabciximaboreptifibatide)givenafterdiagnosticangiography.For
thoseundergoinganinvasiveapproachwhoareatveryhighrisk(eg,recurrent
ischemicdiscomfort,dynamicECGchanges,orhemodynamicinstability),we
consideraddingaGPIIb/IIIainhibitorpriortodiagnosticangiography(either
eptifibatideortirofiban)orafterdiagnosticangiography(abciximabor
eptifibatide).Refertotextfordosing.

Giveanticoagulanttherapyinallpatients:
1.Forpatientsundergoingurgentcatheterization(withinfourhours)or
thosemanagedwithanearlyinvasivestrategy(angiographywithin4to48
hours),weuseeitherheparinorbivalirudin.Wepreferinitiationofheparininthe
emergencydepartmentandaswitchtobivalirudininthecatheterizationlaboratory.
DosingofUFH:IVbolusof60to70units/kgtoamaximumof5000units,
followedbyanIVinfusionof12units/kgperhouradjustedtoachieveagoal
aPTTofapproximately50to70seconds(1.5to2timescontrol).
Doseofbivalirudin:Ifbivalirudinisgivenintheemergencydepartment,IV
bolusof0.1mg/kgandaninfusionof0.25mg/kgperhourbefore
angiography.IfPCIisperformed,anadditional0.5mg/kgbolusisgivenand
theinfusionrateisincreasedto1.75mg/kgperhour.
2.Forpatientsreceivinganoninvasiveapproach,werecommendeither
fondaparinuxorenoxaparin.
EnoxaparinisanalternativetoUFHforpatientsnotundergoinganearly
invasiveapproach.Noloadingdoseisnecessary.Dosingis1mg/kg
subcutaneouslyevery12hours.Doseadjustmentforrenalimpairment(Crcl
<30mL/minute)*:1mg/kgsubcutaneouslyevery24hours.
Fondaparinux:2.5mgsubcutaneouslyevery24hours.Thisdrugshouldbe
avoidedinpatientswithacreatinineclearance<30mL/minute.

Otherimportantconsiderations:
CocainerelatedACS:Givebenzodiazepines(eg,lorazepam2to4mgIVevery15
minutesorso)asneededtoalleviatesymptomsdoNOTgivebetablockers.
StopNSAIDtherapyifpossible.
Correctanyelectrolyteabnormalities,especiallyhypokalemiaandhypomagnesemia,
whichoftenoccurtogether.
ECG:electrocardiogramSTEMI:STelevationmyocardialinfarctionST:STsegmentACS:acute
coronarysyndromeIV:intravenousACLS:advancedcardiaclifesupportBLPAP:bilevelpositive
airwaypressurePCI:percutaneousinterventionTIA:transientischemicattackUFH:
unfractionatedheparinACT:activatedclottingtimeCrcl:creatinineclearanceestimatedusing
CockcroftGaultequation(acalculatorisavailableinUpToDate)aPTT:activatedpartial
thromboplastintimeGP:glycoproteinNSAID:nonsteroidalantiinflammatorydrug.
*Repeateddosesoflowmolecularweightheparintopatientswithrenalinsufficiencymayleadto
accumulationandincreasedriskofbleedingtovaryingdegrees.Incontrast,UFHisnotdependent
primarilyuponrenalfunctionforclearanceandmaybeapreferredoptionforpatientswithCrcl<20
mL/minute,kidneyfailure,orreceivingdialysis.
Graphic75032Version28.0

TIMIgrade3coronaryflowisassociatedwithimproved
survivalafterthrombolysis

IntheGUSTOItrial,the30daymortalityrateafterthrombolysisforacuteST
elevationmyocardialinfarctionvariedwiththedegreeofvesselpatency
achieved.Themortalitywaslowest(4.3percent)inpatientswithTIMIgrade3
(normal)flowintheinfarctrelatedarteryat90minutes.Partialrestorationof
flow(TIMIgrade2)didnotimproveoutcomescomparedtonoororfaintflow
(TIMIgrade0or1).
DatafromTheGUSTOInvestigators.NEnglJMed1993329:673.
Graphic75629Version5.0

Absoluteandrelativecontraindicationstotheuseofthrombolytic
therapyinpatientswithacuteSTelevationmyocardialinfarction*
Absolutecontraindications
Historyofanyintracranialhemorrhage
Historyofischemicstrokewithintheprecedingthreemonths,withtheimportantexception
ofacuteischemicstrokeseenwithinthreehours,whichmaybetreatedwiththrombolytic
therapy
Presenceofacerebralvascularmalformationoraprimaryormetastaticintracranial
malignancy
Symptomsorsignssuggestiveofanaorticdissection
Ableedingdiathesisoractivebleeding,withtheexceptionofmensesthrombolytictherapy
mayincreasetheriskofmoderatebleeding,whichisoffsetbythebenefitsofthrombolysis
Significantclosedheadorfacialtraumawithintheprecedingthreemonths

Relativecontraindications
Historyofchronic,severe,poorlycontrolledhypertensionoruncontrolledhypertensionat
presentiaton(bloodpressure>180mmHgsystolicand/or>110mmHgdiastolicsevere
hypertensionatpresentationcanbeanabsolutecontraindicationinpatientsatlowrisk)
Historyofischemicstrokemorethanthreemonthspreviously
Dementia
Anyknownintracranialdiseasethatisnotanabsolutecontraindication
Traumaticorprolonged(>10min)cardiopulmonaryresuscitation
Majorsurgerywithintheprecedingthreeweeks
Internalbleedingwithintheprecedingtwotofourweeksoranactivepepticulcer
Noncompressiblevascularpunctures
Pregnancy
CurrentwarfarintherapytheriskofbleedingincreasesastheINRincreases
Forstreptokinaseoranistreplaseapriorexposure(morethanfivedayspreviously)or
allergicreactiontothesedrugs
INR:InternationalNormalizedRatio.
*Maynotbeallinclusiveordefinitive.
Datafrom:AntmanEM,AnbeDT,ArmstrongPW,etal.ACC/AHAguidelinesforthemanagementof
patientswithSTelevationmyocardialinfarctionexecutivesummary:areportoftheAmerican
CollegeofCardiology/AmericanHeartAssociationTaskForceonPracticeGuidelines(Writing
CommitteetoRevisethe1999GuidelinesfortheManagementofPatientsWithAcuteMyocardial
Infarction).Circulation2004110:588.
Graphic68784Version9.0

Cooperativecardiovascularprojectriskmodelforintracranial
hemorrhagewiththrombolytictherapy
RiskFactors*
Age75years
Blackrace
Femalesex
Priorhistoryofstroke
Systolicbloodpressure160mmHg
Weight65kgforwomenor80kgformen
INR>4orPT>24
Useofalteplase(versusotherthrombolyticagent)

Riskscore

Rateofintracranialhemorrhage,
percent

0or1

0.69

1.02

1.63

2.49

4.11

*Eachriskfactorisworth1pointifpresent,0pointsifabsent.Pointsareaddedtodeterminethe
riskscore.
INR:internationalnormalizedratioPT:prothrombintime.
DatafromBrassLM,LichtmanJH,WangY,etal.Intracranialhemorrhageassociatedwith
thrombolytictherapyforelderlypatientswithacutemyocardialinfarction:resultsfromthe
cooperativecardiovascularproject.Stroke200031:1802.
Graphic62946Version6.0

PreferredthrombolyticregimensforacuteSTelevationmyocardial
infarction
Drug
Alteplase
(accelerated
regimen)

Recommended
IVregimen*
15mgbolus
then0.75mg/kg
(maximum50mg)
over30minutes

Advantagesandlimitations
BetteroutcomesthanstreptokinaseinGUSTO1(30
daymortality6.3versus7.3percent)costlierthan
streptokinasemoredifficulttoadministerbecauseof
shorthalflife

then0.5mg/kg
(maximum35mg)
overthenext60
minutes
Tenecteplase

Singlebolusover
fivetotenseconds
baseduponbody

AseffectiveasalteplaseinASSENT2withless
noncerebralbleedingandneedfortransfusioneasier
toadminister(singlebolusduetolongerhalflife)both

weight:

inandoutofhospitaltheseadvantagesmake
tenecteplasethedrugofchoiceinmanyUShospitals

<60kg:30mg
60to69kg:35
mg
70to79kg:40
mg
80to89kg:45
mg
90kg:50mg
Reteplase

10unitsovertwo
minutesthenrepeat
10unitbolusat30

Similaroutcomesasalteplasebuteasiertoadminister

minutes
Streptokinase

1.5millionunits
over30to60
minutes

Generallyamuchlesscostlyoptionthanother
fibrinolyticsbutoutcomesareinferior.Neutralizing
antibodiesdevelop,whichcandiminishefficacyof
subsequentuse.Elevatedriskofhypersensitivity
reactionwithrepeateddoses.Usedextensivelyoutside
NorthAmericaduetolowercost.(NotavailableinUS
orCAN).

*Allpatientsarealsogivennonentericcoatedaspirin162to325mgand,withalteplase,
reteplase,andtenecteplase,unfractionatedheparinasa60units/kgbolus(maximum4000units)
followedbyanintravenousinfusionof12units/kgperhour(maximum1000unitsperhour)
adjustedtotargetaPTTof50to70seconds.Heparinhasnotbeendefinitivelyshowntoimprove
outcomeswithnonfibrinspecificagentssuchasstreptokinase.However,heparinisrecommended
withstreptokinaseinpatientswhoareathighriskforsystemicthromboembolism(largeoranterior
myocardialinfarction,atrialfibrillation,previousembolus,orknownleftventricularthrombus).
Graphic56744Version4.0