MKSAP17

CardiovascularMedicine
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Chapter03:CoronaryArteryDisease
RelatedQuestions
Previous:DiagnosticTestinginCardiology

CoronaryArteryDisease

StableAnginaPectoris
DiagnosisandEvaluation
RelatedQuestion
Question118
Themostcommonmanifestationofcoronaryarterydisease(CAD)isstableanginapectoris:chest
pain,pressure,ordiscomfortthatdevelopswithexertionandisrelievedwithrest.Symptomsoften
occurwhentheburdenofatheromatousplaqueresultsinfixedcoronarystenosisandlimitationof
bloodflow,leadingtoanimbalancebetweenmyocardialoxygensupplyanddemand.Whenpatients
withcardiovascularriskfactorspresentwithchestpain,thelocationofthepain,qualityofsymptoms
(sharp/dull,transient/persistent,occurringatrest/withexertion),andtheageandsexofthepatientcan
helptodifferentiatestableanginapectorisfromothercausesofchestpain,suchasgastrointestinal,
musculoskeletal,orpulmonarycauses.Thesefactorsarealsousedtodetermineapatient'spretest
likelihoodofCAD(Table8).
ThedecisiontoperformexerciseorpharmacologicstresstestingorcoronaryCTangiography(CTA)
isbasedonthepretestlikelihoodofCAD,thepatient'sbaselineelectrocardiogram(ECG),the
patient'sabilitytoexercise,andthepatient'scomorbidillnesses,suchasasthmaoremphysema,that
wouldlimitpharmacologictesting(Figure5).Theselectionoftestsforevaluatingpatientswithchest
painisdiscussedinDiagnosticTestinginCardiology.Stresstestingismostusefulinpatientsat
intermediatepretestlikelihoodofCAD(10%to90%).Inpatientswithlowpretestprobability,a
normaltestresultonlyconfirmsthatthepatientislowrisk,andanabnormalstresstestresultismost
likelyafalsepositive,possiblyleadingtomoretesting(additionalstresstestingorinvasive
angiography).Inpatientswithahighpretestlikelihood,theuseofstresstestingfordiagnostic
purposesisnotindicated,asanabnormaltestresultonlyconfirmsthepresenceofdiseaseanda
normaltestresultismostlikelytoindicateafalsenegativeresult.
Stresstestinginpatientswithhighpretestlikelihoodcanbeusedtoobtainprognosticinformation,but
theresultsshouldnotaffecttheinitiationofoptimalmedicaltherapy.Inpatientswhohavebeen
startedonmedicaltherapyforCAD,stresstestingcanbeusedtodetermineapatient'sresponseto
optimalmedicaltherapy,measureexercisecapacity,andevaluatetheextentandseverityofischemia.
ThedevelopmentofcoronaryCTAisanemergingalternativetostresstesting,butcoronaryCTAdoes
notprovideimportantfunctionalinformation,suchasextentofischemia,reproductionofsymptoms,
orexercisecapacity.CoronaryCTAisusefulfordiagnosticpurposesinpatientsatintermediaterisk
forCADifstresstestingiscontraindicatedorrevascularizationisunlikelytobeperformedorchange
management.

Theuseofinvasivecoronaryangiographyinpatientswithstableanginapectorisisgenerallylimited
tothosewithpersistentorprogressivelifelimitingsymptomswhileonoptimalmedicaltherapyor
thosewithhighriskcriteriaonnoninvasivestresstestingorcoronaryCTA(seeFigure5).

KeyPoints
Whenpatientswithcardiovascularriskfactorspresentwithchestpain,thequalityofsymptoms,
theage,andthesexofthepatientcanhelptodifferentiatestableanginapectorisfromother
causesofchestpain.
Stresstestingismostusefulinpatientsatintermediatepretestlikelihoodofcoronaryartery
disease(10%to90%).

GeneralApproachtoTreatmentofStableAnginaPectoris
Allpatientswithischemicheartdiseaseshouldbecounseledontheimportanceofriskfactor
modification,includinglifestylechanges,suchassmokingcessation,weightmanagement,daily
physicalactivity,anddietmodificationaswellascontrolofmodifiableriskfactors,suchasdiabetes
mellitus,hypertension,andhyperlipidemia.Medicaltherapyshouldbeinitiatedinallpatientswith
ischemicheartdisease.Thecombinationofriskfactormodificationandmedicaltherapyisreferredto
asguidelinedirectedmedicaltherapy(Figure6).Medicaltherapyisdividedintotwocategories:
cardioprotectivemedicationsandantianginalmedications.Cardioprotectivemedicationsimprove
survival,reducetheoccurrenceofcardiovascularevents,andreducetheprogressionofsystemic
atherosclerosis.Antianginalmedicationsvasodilatethecoronaryvasculatureordecreasemyocardial
oxygendemand,thusreducingthefrequencyandseverityofanginapectorisandimprovingqualityof
life.
CardioprotectiveMedications
RelatedQuestion
Question13
Theuseofaspirinisassociatedwithadecreasedriskofmyocardialinfarction,stroke,and
cardiovasculardeathinpatientswithCAD.Aspirindosesof81mgto162mgdailyarerecommended
inallpatientswithestablishedCADunlesscontraindicated.Inpatientsallergictoaspirin,clopidogrel
isrecommendedasanalternative.Theuseofnewerantiplateletagents(prasugrel,ticagrelor)as
monotherapyhasnotbeentestedinpatientswithstableanginapectoris.Dualantiplatelettherapy
(aspirinpluseitherclopidogrel,prasugrel,orticagrelor)iscurrentlyrecommendedonlyfollowing
percutaneouscoronaryintervention(PCI)oranacutecoronaryevent.
Owingtotheprotectiveeffectsofblockers,theseagentsareconsideredfirstlinetherapyinpatients
withstableanginapectoris.Dosetitrationofblockersisrecommendeduntiltherestingheartrateis
between55/minand60/min.Blockershavebeenassociatedwithfatigue,reducedexercisecapacity,
symptomaticbradycardia,mooddisturbance(depression),anderectiledysfunction.Blockersare
contraindicatedinpatientswithsymptomaticbradycardia,highgradeatrioventricularblock,acute
decompensatedheartfailure,andseverereactiveairwaysdisease.
ACEinhibitorsareindicatedinthetreatmentofpatientswithstableanginapectoristoreduce
cardiovascularandallcausemortality.Thiseffectonmortalityismoreprofoundinpatientswith
concomitantdiabetesmellitusandleftventricularsystolicdysfunction.Additionally,ACEinhibitors
areindicatedinpatientswithconcomitantsystemichypertensionandproteinuricchronickidney
disease.ACEinhibitorsarecontraindicatedinpregnantwomenandcautionisadvisedinpatientswith
advancedchronickidneydisease.Angiotensinreceptorblockersareconsideredacceptable

alternativesinpatientswhoareallergictoorintolerantofACEinhibitors.
Statinshavebeenshowntoreducetheriskofmyocardialinfarctionanddeathinpatientswithchronic
ischemicheartdiseaseby25%to30%.Thereductionincardiovasculareventsisproportionaltothe
degreeofLDLcholesterolreductionhowever,statinshavebeenprovedtobebeneficialinpatients
regardlessofcholesterollevel.Newcholesterolmanagementguidelinesrecommendtheuseof
moderatetohighintensitystatinsforallpatientswith(1)LDLcholesterollevelof190mg/dL(4.92
mmol/L)orgreater(2)diabetesmellitusor(3)greaterthan7.5%estimated10yearriskof
atheroscleroticcardiovasculardisease(ASCVD).Managementofstatintherapyisdiscussedin
MKSAP17GeneralInternalMedicine.
AccordingtoAdvisoryCommitteeonImmunizationPractices(ACIP)guidelines,allpersonsaged6
monthsoroldershouldhaveanannualinfluenzavaccination.Inaddition,patientsatriskfor
cardiovasculardiseasewarrantinfluenzavaccinationasapreventivemeasureforcardiovascular
disease.
Theuseofselenium,chromium,carotene,vitaminC,vitaminE,andestrogenhasnotbeen
associatedwithimprovedcardiovascularoutcomesandisnotrecommendedinpatientswithischemic
heartdisease.
AntianginalMedications
RelatedQuestion
Question11
Medicationstoreducethefrequencyandseverityofanginapectoriscompriseblockers,nitrates,
calciumchannelblockers,andranolazine.
Blockersandnitratesarefirstlineantianginalagents.Inadditiontotheircardioprotectiveeffects,
blockersimproveanginapectorisbyreducingheartrate,myocardialcontractility,andbloodpressure,
resultinginreducedmyocardialoxygendemand.Nitratesimprovemyocardialoxygensupplyand
reducemyocardialoxygendemandbytheireffectsoncoronaryandsystemicvasodilation,
respectively.Nitrateshavenotbeenprovedtoreducethefrequencyofcardiovascularevents
(myocardialinfarction,death).Twocategoriesofnitratesareindicatedforpatientswithstableangina
pectoris:sublingualorspraynitroglycerin(foremergencyuse)andtopicalororalnitroglycerin(for
chronic,dailyuse).Theuseofdailynitratesrequiresperiodicnitratefreeintervals(typicallyatnight)
toavoidthedevelopmentoftolerance.Themostfrequentadverseeffectofnitratesisheadache.The
useofeithershortorlongactingnitratesiscontraindicatedinpatientswhotakephosphodiesterase5
(PDE5)inhibitorsforerectiledysfunction(sildenafil,vardenafil,tadalafil)owingtothepotentiation
ofhypotensionwhenthesedrugsareusedtogether.
Calciumchannelblockersaresecondlinetherapyinpatientswithstableanginapectoriswhoare
intolerantofblockersorwhohavecontinuedsymptomsonblockersandnitrates.Allcalcium
channelblockerscausesystemicandcoronaryvasodilation,andnondihydropyridinecalciumchannel
blockers(diltiazem,verapamil)reducetheheartrate.Becauseoftheirvasodilatoryproperties,calcium
channelblockersarefirstlineagentsforthemanagementofpatientswithPrinzmetal(variant)angina
pectoris.Themostcommonadverseeffectsofcalciumchannelblockersareperipheraledema,
dizziness,constipation,andbradycardia.Calciumchannelblockersarecontraindicatedinpatients
withleftventricularsystolicdysfunctionoradvancedatrioventricularblock.
Ranolazineisaselectiveinhibitorofthelateinwardsodiumchannelinthemyocardium.Itis
generallyreservedforpatientswhoremainsymptomaticwiththeuseofblockers,nitrates,and
calciumchannelblockers.Ranolazineisaneffectiveantianginalmedicationhowever,itsuseis

limitedbycostandadverseeffectssuchasdizziness,headache,nausea,andconstipation.Ranolazine
shouldbeusedwithcautioninpatientswithadvancedkidneyorliverdiseaseandinthosetaking
medicationsthatarepotentinhibitorsoftheCYP3A4pathway.Examplesofstronginhibitorsofthe
CYP3A4pathwayincludeketoconazole,clarithromycin,tacrolimus,andcyclosporine.

KeyPoints
Aspirinorclopidogrel(ifaspirinallergic)isrecommendedinallpatientswithestablished
coronaryarterydiseaseunlesscontraindicatedtheuseofnewerantiplateletagents(prasugrel,
ticagrelor)asmonotherapyhasnotbeentestedinpatientswithstableanginapectoris.
Allpatientswithstableanginapectorisshouldreceiveastatinandablocker.
ACEinhibitorsareindicatedinthetreatmentofstableanginapectoris,particularlyinpatients
withconcomitantdiabetesmellitusandleftventricularsystolicdysfunction.

CoronaryRevascularization
DecisiontoRevascularize
RelatedQuestion
Question48
Inpatientswithstableanginapectoriswhosesymptomsarenotimprovedwithoptimalmedical
therapy,invasiveangiographyiswarrantedtodefinecoronaryarteryanatomyandpreparefor
revascularizationviaPCIorcoronaryarterybypassgraftsurgery(CABG).Allpatientsshouldbe
counseledontherisks,benefits,andalternativestoangiographyandrevascularizationbefore
diagnosticangiographyispursued.
InpatientsfoundtohavesignificantCADonangiographythatwouldbenefitfromrevascularization,
multiplefactorsareconsideredindecidingwhichtechnique(PCIorCABG)wouldbebestforthe
patient.Theseincludethedegreeofleftventricularsystolicdysfunction,whetherthepatienthashada
priorCABG,andthepatient'sabilitytoadheretoamedicationtreatmentregimen.TheSYNTAX
scoreisananatomicscoringsystembasedontheresultsofangiographythatquantifieslesion
complexityinpatientswithmultivesseland/orleftmaincoronaryarterydiseaseandisusefulin
helpingpredicttheoutcomeofdifferentrevascularizationstrategies.Thedevelopmentofappropriate
usecriteria(AUC),acollectionofclinicalscenariosthatmimicfrequentlyencounteredpatient
presentations,hasassistedcliniciansinmakingtreatmentdecisionsforpatientswithallformsof
ischemicheartdisease.
PercutaneousCoronaryIntervention
PCIhasnotbeenshowntobesuperiortooptimalmedicaltherapyinpatientswithstableangina
pectorisforreductionofcardiovascularendpointssuchasmortalityandmyocardialinfarction.
However,PCIhasbeenassociatedwithimprovementinqualityoflifebyreducingtheseverityand
frequencyofangina.CurrentguidelinesrecommendthatdiagnosticangiographyandPCIbereserved
forpatientswithrefractorysymptomswhileonoptimalmedicaltherapy,thosewhoareunableto
tolerateoptimalmedicaltherapyowingtosideeffects,orthosewithhighriskfeaturesonnoninvasive
exerciseandimagingtests.
CoronaryArteryBypassGraftSurgery
RelatedQuestion

Question18
TheuseofCABGinpatientswithstableanginaisgenerallyindicatedonlyforthosewhoremain
symptomaticwithoptimalmedicaltherapyandhavespecificangiographicfindings(eitherleftmain
diseaseormultivesseldiseasewithinvolvementoftheproximalleftanteriordescendingartery),
concomitantreducedsystolicfunction,ordiabetesmellitus.CABGistypicallyperformedviamedian
sternotomyincisionandinstitutionofcardiopulmonarybypasshowever,recentadvanceswithoff
pumpCABGallowpatientstoavoidtheneedforcardiopulmonarybypass.OffpumpCABGis
associatedwithadverseeventandgraftpatencyratessimilartotraditionalCABG.Thislessinvasive
proceduremaybemoresuitableforpatientswithsignificantcomorbidmedicalconditionsasitmay
reduceoperativeriskandshortenhospitalandrecoverytimes,butdefinitiveproofislacking.
AfterRevascularization
Thelongtermgoalsoftherapyforischemicheartdiseasearetomaximizequalityoflifeandexercise
functionandminimizemorbidityandmortality.Clinicalpracticeguidelinesdonotrecommendthe
routineuseofECGmonitoring,stresstesting,oranatomictesting(coronaryCTAorinvasive
angiography)inasymptomaticpatientsafterPCIorCABG.
AllpatientswithstableanginapectoriswhoundergoPCIorCABGshouldbetreatedwithaspirin(81
162mg/d)indefinitely.InpatientswhoundergoPCI,dualantiplatelettherapy(aspirinplus
clopidogrel)isrecommendedforatleast1monthafterbaremetalstent(BMS)implantationandat
least1yearafterdrugelutingstent(DES)implantation,althoughextendedusecanbeconsideredon
anindividualbasisifapatient'sischemicriskishighandbleedingriskislow(Table9).Amajorrisk
withprematurediscontinuationofdualantiplatelettherapyistheoccurrenceofstentthrombosis,a
complicationwithhighmorbidityandmortality.
InpatientswhoundergoCABG,preoperativecardioprotectiveandantianginalmedicationsshouldbe
continuedindefinitely.Thebenefitofcardioprotectivemedications(aspirin,blockers,ACE
inhibitors,statins)isgreatestinpatientswithhighriskfeaturessuchasreducedleftventricular
systolicfunction,priormyocardialinfarction,chronickidneydisease,ordiabetes.

KeyPoints
Percutaneouscoronaryinterventionimprovesanginasymptomsandqualityoflifeinpatients
withstableanginapectorisbutdoesnotincreasesurvivalorreducefuturecardiovascular
events.
Forstableanginapectoris,percutaneouscoronaryinterventionisreservedforpatientswith
refractorysymptomswhileonoptimalmedicaltherapy,thosewhoareunabletotolerateoptimal
medicaltherapyowingtosideeffects,orthosewithhighriskfeaturesonnoninvasiveimaging.
ClinicalpracticeguidelinesdonotrecommendtheroutineuseofECGmonitoring,stress
testing,oranatomictesting(coronaryCTangiographyorinvasiveangiography)in
asymptomaticpatientsafterpercutaneouscoronaryinterventionorcoronaryarterybypassgraft
surgery.
Inpatientswithstableanginapectoriswhoundergopercutaneouscoronaryintervention,dual
antiplatelettherapy(aspirinplusclopidogrel)isrecommendedforatleast1monthafterbare
metalstentimplantationandatleast1yearafterdrugelutingstentimplantation.

AcuteCoronarySyndromes
GeneralConsiderations

Acutecoronarysyndrome(ACS)encompassesSTelevationmyocardialinfarction(STEMI)andnon
STelevationacutecoronarysyndromes(NSTEACSs),whichcomprisenonSTelevationmyocardial
infarction(NSTEMI)andunstableangina(UA)(Figure7).ThepathophysiologyofACSismost
commonlycharacterizedbyplaquerupture(75%ofcases)andplaqueerosion(25%ofcases).STEMI
iscausedbyacompleteocclusionofanepicardialcoronaryarterybythrombusatthesiteofplaque
disruptionandisdefinedbythepresenceofischemicchestpain(oranequivalent)andthepresenceof
greaterthan1mmSTsegmentelevationintwoormoreconsecutiveleadsornewleftbundlebranch
blockonECG.STsegmentdepressionintwoormoreprecordialleads(V1throughV4)mayindicate
transmuralposteriorinjury.InUAandNSTEMI,theocclusionisincomplete.NSTEACSsare
characterizedbythepresenceofischemicchestpain(oranequivalent),thenotableabsenceofST
segmentelevationonECG,andthepresenceofeitherSTsegmentdepressionorTwaveinversionon
ECG.InNSTEMI,cardiacbiomarkers(serumcreatinekinaseMBandtroponin)areabnormal,
whereasinUA,cardiacbiomarkersarenormal.
BecausetheaffectedarteryiscompletelyoccludedinSTEMI,itsdiagnosisandtreatmentare
markedlydifferentfromthoseofUAorNSTEMI.Forthisreason,aninitialECGisimperativeinall
patientspresentingwithsymptomsconsistentwithischemicchestpain,andoncediagnosisofSTEMI
occurs,emphasisisplacedonimmediatereperfusionofthevesselviathrombolytictherapyorPCI.
PatientswithischemicchestpainbutwithoutSTsegmentelevationoninitialECGaretypically
classifiedashavingNSTEACSandthenundergolaboratorytestingforcardiacbiomarkers.Because
thesepatientsdonothaveanECGconsistentwithcompleteocclusionofacoronaryarteryand
becausethisgroupofpatientsisheterogeneous,riskstratificationshouldoccurpriortoconsideration
ofcoronaryangiographyandsubsequentcoronaryrevascularizationwithPCIorCABG.

STElevationMyocardialInfarction
Recognition
OptimalmanagementandimprovedoutcomesinpatientswithSTEMIdependonearlyrecognition
andinstitutionofreperfusiontherapywitheitherthrombolysisorprimaryPCI(Figure8).Overthe
pastdecade,varioussystemsbasedinterventionshaveprovedeffectiveinincreasingthepercentageof
patientsdiagnosedatthetimeofhospitalpresentation,reducingthetimerequiredtoreperfusean
occludedbloodvesselwitheitherthrombolysisorPCIandreducingtransfertimetoafacilitycapable
ofthrombolysisorPCI.
STEMIisdiagnosedclinicallybasedontheinitialECGandthepresenceofischemicchestpain.
Severalconditionsshouldbeconsideredinthedifferentialdiagnosisatthetimeofpresentation,
particularlyacuteaorticdissection,pulmonaryembolism,andpericarditis.Afocusedhistoryshould
betakentodeterminethepatient'squalityanddurationofsymptoms,riskfactorsforCAD,prior
historyofPCIorCABG,andbleedingriskasitpertainstoreperfusiontherapy.Physicalexamination
isimperativetoevaluateforconditionsthatmimicSTEMI,includingacuteaorticdissection
(asymmetricarmpressures)andpericarditis(pericardialrub).Physicalexaminationshouldalsolook
forsignsofSTEMIcomplications,suchashypotension(ventricularwallrupture,cardiogenicshock)
andheartmurmur(acutemitralregurgitation).Finally,thephysicalexaminationisimportanttoassess
forfactorsthatmayinfluencetreatmentoptions(gastrointestinalbleeding,neurologicdeficits,heart
failure,coagulopathy).
Reperfusion
RelatedQuestions
Question42
Question61

Question92
ReperfusionforpatientswithSTEMIoccursprimarilyviathrombolytictherapyandprimaryPCI.
Despiteearlysuccesswiththrombolytictherapy,somestudiessuggestthat30%to50%ofpatients
receivingthrombolysisdonotachievecompletereperfusion.Factorsthatmustbeconsideredwhen
decidingtoadministerthrombolysisorperformprimaryPCIincludetheavailabilityofaPCIcapable
facility,timefromonsetofsymptomstopresentation,thepresenceofhighriskfeatures,andrelative
orabsolutecontraindicationstothrombolytictherapy(Table10).Thepreferredmethodofreperfusion
isprimaryPCI,especiallyforpatientspresentingtohospitalswithonsitePCIfacilities.Becausemany
patientswithSTEMIpresenttohospitalswithoutonsitePCIfacilities,atreatmentalgorithmis
typicallyinplacetoemergentlytransferpatientstoaPCIcapablefacilityoradministerfulldose
thrombolytictherapy.Evenwhenthrombolytictherapyisadministered,treatmentguidelines
recommendthatpatientsbetransferredtoaPCIcapablefacilitybecauseofthepotentialfor
thrombolyticfailure.
InpatientswhoundergoprimaryPCI,thetimefrompatientpresentationtodevicedelivery(balloon
inflationorthrombectomycatheteractivation)isamajordeterminantofimprovedoutcomesobserved
inprimaryPCIwhencomparedwiththrombolysis.Severalstudieshavedemonstratedsuperior
efficacyoftransferforprimaryPCIversusthrombolytictherapyhowever,observationalstudieshave
reportedthatpatientsoftenexperiencedelaysintransferforprimaryPCIthatexceed1hour.When
PCIcannotbereadilyachievedwithin120minutes,thrombolytictherapyisrecommendedinthose
patientswithoutcontraindications.Regionalandnationaleffortshaveimprovedthesetransfer
procedurestoincludetheabilityofemergencymedicalservices(EMS)toperformECGinthefield,
immediatetransferofpatientstoPCIcapablefacilitieswhenSTEMIisrecognized,andimproved
communicationbetweennonPCIfacilitiesandPCIfacilities.
Table11showsthecharacteristicsofthemostcommonlyusedthrombolyticagentsthatarecurrently
available.Althoughlifethreateningbleedingevents,suchasintracerebralhemorrhage,arerare,they
carryanextremelyhighmortalityrate(50%60%).Patientstreatedwiththrombolytictherapyshould
becloselyobservedclinicallyforsymptomresolutionandreperfusionarrhythmias,especiallyan
acceleratedidioventricularrhythm(AIVR)AIVRisconsideredabenignrhythmwhenitoccurs
within24hoursofreperfusion.ArepeatECGshouldbeobtained60minutesafterthrombolysisto
determineifSTsegmentresolutionhasoccurred.
Thrombolyticfailureoccursinapproximately30%ofpatients,andtypicallypresentswithfailureto
fullyresolvechestpainorimproveSTsegmentelevationby50%somepatientsmayshow
hemodynamicinstabilityorventriculararrhythmias.Inthesecircumstances,rescuePCIisindicated.
RescuePCIisassociatedwithimprovedcardiovascularoutcomeswhencomparedwithconservative
medicaltherapyinpatientswithfailureofthrombolytictherapy.FacilitatedPCIistheadministration
offullorhalfdosethrombolytictherapy(withorwithoutaglycoproteinIIb/IIIainhibitor)followed
byplanned,immediatePCI.Adverseevents(especiallybleeding)havelimitedthesafetyandoverall
useoffacilitatedPCI.
MedicalTherapy
RelatedQuestion
Question81
Atthetimeofinitialpresentation,allpatientswithSTEMIshouldbegivena325mgloadingdoseof
aspirin,supplementaloxygen,therapytoimprovesymptoms(nitrates,analgesics),therapytoreduce
infarctsize(blockers,ACEinhibitors),andantithrombotictherapy(antiplateletagents,
anticoagulants).Aspirinshouldbeadministeredimmediatelyhowever,theadministrationofother
agentsshouldnotdelaytheplantoreperfusetheinfarctrelatedartery.

InmanypatientswithSTEMI,controlofchestpaincanbeachievedwithsublingualorintravenous
nitrates.Morphineandotheropioidanalgesicsarealsoeffectiveforreducingchestpainbydecreasing
thebody'ssympatheticresponsetoSTEMI.CautionshouldbeusedinpatientswithinferiorSTEMI
andevidenceofrightventricularinfarctionbecausenitratesandanalgesicscanleadtoreduced
preloadandsignificanthypotension.
InthetreatmentofSTEMI,blockersarerecommendedatthetimeofinitialpresentationexceptin
patientswithevidenceofheartfailure,hypotension,bradycardia,advancedatrioventricularblock,or
othercontraindicationstoblockers.Intravenousmetoprololisthemostwidelyusedblockerfor
STEMItreatmentitisdosedin5mgincrementsevery5minutes,foratotaldoseof15mg.
Followingreperfusion,anoralblockerisrecommendedtoreducemyocardialoxygendemandand
reducemortality.
ACEinhibitorsshouldbeadministeredafterreperfusioninallpatientswithoutcontraindications
(systolicbloodpressure<90mmHg,advancedkidneydysfunction,hyperkalemia).Angiotensin
receptorblockersmaybesubstitutedinpatientswhoareallergicorintoleranttoACEinhibitors.
TheuseofantiplateletagentsinthesettingofSTEMIhaschangedoverthepastdecadewiththe
availabilityofseveralnewagents.AspirinremainsamainstayinthetreatmentofACSandshouldbe
administeredtoallpatientsunlessallergicorintolerant.PlateletP2Y12receptorinhibitorsimpair
plateletaggregation,andthiseffectisadditivetoaspirin.Availableagentsincludeclopidogrel,
ticagrelor,andprasugrel.Clopidogrelhasbeenthemostwidelystudied,anditsusewithconcomitant
thrombolytictherapyandprimaryPCIisassociatedwithimprovedoutcomesandnoapparentincrease
intheriskofbleeding.ForpatientsforwhomprimaryPCIfortreatmentofSTEMIisplanned,both
ticagrelorandprasugreldemonstratedsuperiorefficacywhencomparedwithclopidogrelhowever,
veryfewpatientsinthesestudiesweretreatedwiththrombolytictherapy,andlittleevidenceexiststo
recommendtheuseofeitherticagrelororprasugrelinpatientsreceivingthrombolytictherapy.Dual
antiplatelettherapyshouldbecontinuedinSTEMIpatientsforafullyear,regardlessofintervention
orstentusedhowever,ifdualantiplatelettherapycannotbemaintainedforafullyear(forexample,
becauseofbleeding,needforsurgery,orproblemswithadherence)andthepatienthasabaremetal
stentimplanted,aminimumof4weeksofdualantiplatelettherapyisadvised.
PlateletglycoproteinIIb/IIIainhibitors(abciximab,tirofiban,eptifibatide)furtherinhibitplatelet
aggregationandimpairplateletactivation.TheyareusefulinpatientswithSTEMIwhoundergo
primaryPCIhowever,theuseofglycoproteinIIb/IIIainhibitorsshouldbereservedforadministration
inthecatheterizationlaboratoryratherthanupfrontintheemergencydepartmentowingtothe
increasedriskofbleedingandnoclearbenefitwhenadministeredpriortoprimaryPCI.Routine
glycoproteinIIb/IIIainhibitoruseinpatientswhoreceivethrombolytictreatmentwithoutPCIis
controversialandnotcurrentlyrecommended.
ThechoiceofanticoagulantfortreatmentofSTEMIisdependentonthereperfusionstrategyavailable
forthepatient.Unfractionatedheparin(UFH)hasbeenthoroughlystudiedinpatientsreceiving
thrombolyticagents,anditsuseisassociatedwithareducedincidenceofreocclusionoftheinfarct
relatedartery.Lowmolecularweightheparin(LMWH)hasalsobeenassociatedwithimproved
outcomesinpatientswhoreceivethrombolytictherapy.InpatientsundergoingprimaryPCI,theuse
ofUFHisfavoredoverLMWHowingtotheabilitytomonitorthedegreeofanticoagulation(by
measurementofactivatedclottingtimes).WhenaheparinbasedstrategyisutilizedforprimaryPCI,
guidelinesrecommendtheconcomitantadministrationofaglycoproteinIIb/IIIainhibitor.Recent
studiesofbivalirudin,adirectthrombininhibitor,haveshownthatitsuseatthetimeofprimaryPCIis
associatedwithasimilarrateofischemicevents(death,myocardialinfarction,stroke,stent
thrombosis)andfewerbleedingeventswhencomparedwithaheparinplusglycoproteinIIb/IIIa
inhibitor.Ingeneral,therapiesthatreducebleedingcomplicationsmayimprovesurvivalbutwith
concernforgreaterriskofnonfatalischemicevents,suchasearlystentthrombosis.

InpatientswithdiabetesmellituswhopresentwithSTEMI,plasmaglucoselevelsshouldbe
maintainedbelow180mg/dL(10.0mmol/L)whileavoidinghypoglycemia.Intravenousinsulinhas
beentestedinmultipletrials,butneitherintravenousinsulinnorglucoseinsulinpotassiuminfusions
arerecommendedcurrently.
ComplicationsofSTEMI
RelatedQuestions
Question63
Question105
ThemostcommoncomplicationsduringtheearlymanagementperiodafterSTEMIarearrhythmias,
heartfailure,andvascularaccessissuesinpatientswhoundergoprimaryPCI.Asmanyas75%of
patientswithSTEMIhaveanarrhythmiaduringhospitalization,includingatrialandventricular
arrhythmias,sinusbradycardia(afterinferiorwallmyocardialinfarction),atrioventricularblock,and
sinustachycardia(afteranteriorwallmyocardialinfarction).Approximately10%to15%ofpatients
haveatrialfibrillationorflutterduringhospitalization,andthisisassociatedwithpoorerlongterm
outcomes.Thepresenceofatrialfibrillationorheartblockisoftentransientinpatientswithinferior
wallmyocardialinfarctionandsuggestiveofmoreextensiveinfarctioninpatientswithanteriorwall
myocardialinfarction.Ventriculararrhythmias(ventriculartachycardia,ventricularfibrillation)that
occurinthefirst24hoursafterSTEMIdiagnosisdonottypicallyaffectprognosis,require
antiarrhythmicmedications,orrequiredefibrillatorimplantation.Theoccurrenceofrecurrent
ventriculararrhythmiaslaterinhospitalizationisassociatedwithalargerinfarctandhighershortand
longtermmorbidityandmortality.Inpatientswithpersistenthighdegreeatrioventricularblockor
symptomaticbradycardia,placementofatemporarytranscutaneousortransvenouspacemakermaybe
neededtodeterminereversibilityorbenefitofpermanentpacemakerimplantation.
Theseverityofheartfailure(rangingfromasymptomaticleftventricularsystolicdysfunctionto
cardiogenicshock)isdependentontheextentofmyocardialinfarction,severityofobstructiveCAD,
timefromsymptomonsettoreperfusion,andpatientspecificfactors(age,comorbidconditions).
PatientswhodevelopcardiogenicshockafterSTEMIoftenhavemoreextensiveleftventricular
infarctionandanelevatedinpatientmortalityrategreaterthan60%,thuspromptingaggressive
medicaltherapyandhemodynamicsupportwithintraaorticballooncounterpulsation.Theinitiation
oftherapytoreducepreload(diuretics)andafterload(nitrates,ACEinhibitors)isindicatedinall
patientswithsymptomsofheartfailurehowever,cautionisadvisedifsystolicbloodpressureisless
than90mmHgorkidneydysfunctionexists.
Vascularaccesscomplicationsincludehematoma,pseudoaneurysm,arteriovenousfistula,and
retroperitonealhemorrhage.
MechanicalcomplicationsinSTEMIpatients(Table12)aremuchlessfrequentinthereperfusion
era.Rightventricularinfarction,whichmostcommonlyresultsfromocclusionoftheproximalright
coronaryartery,shouldbeconsideredinallpatientswithinferiorwallmyocardialinfarctionand
hypotension.Rightventricularinfarctionleadstodecreasedpulmonarybloodflowandleftatrial
return,decreasedpreload,andimpairedfillingoftheleftventricle.Thisresultsinthetriadof
hypotension,clearlungexamination,andelevatedjugularvenouspressure.Diagnosisisoftenmade
clinicallyandcanbeconfirmedbyeitherECG(leadsV4RthroughV6R)orechocardiography(often
usedtoexcludeothercausesofcardiogenicshock).Treatmentconsistsofreperfusion,aggressive
volumeresuscitation,andtheuseofinotropes(dopamineordobutamine)untilrightventricular
functionimproves(often2to3daysaftermyocardialinfarction).
AventricularseptaldefectisaninfrequentcomplicationofSTEMI.Itmanifestsashemodynamic
compromiseinthesettingofanewloudholosystolicmurmurandoftenapalpablethrill3to7days

aftertheinitialmyocardialinfarction.Diagnosisismostcommonlymadebytransthoracic
echocardiography.Medicalstabilizationgenerallyrequirestheadministrationofvasopressoragents
andplacementofanintraaorticballoonpump.Althoughsurgicalmortalityishigh,inpatientmortality
forpatientswhodonotundergosurgeryisnearly100%.Percutaneousventricularseptaldefect
closuredevicesaresometimesusedinnonsurgicalpatients,buttheiruseislimitedbyanatomyand
operatorexpertise.
MitralregurgitationoccurscommonlyafterSTEMI.Mechanismsincludesevereleftventricular
dysfunctionwithannulusdilatation,worseningofpreexistingmitralregurgitation,andcompromise
ofthemitralapparatus(ruptureofpapillarymuscleorchordaetendineae).Papillarymusclerupture
oftenpresents3to7daysafterinitialmyocardialinfarctionwithhemodynamiccompromise,
pulmonaryedema,andaloudsystolicmurmur.Diagnosisismostoftenmadebytransthoracic
echocardiography,andtransesophagealechocardiographymayberequiredtoplansurgical
reconstruction.Treatmentconsistsoftheadministrationofvasodilatorstoreduceafterloadand
diureticstodecreasepreload.Ifpatientsbecomehemodynamicallycompromised,theadministration
ofvasopressors,placementofanintraaorticballoonpump,and/orsurgicalinterventionarerequired.
LeftventricularfreewallruptureisthemostominousmechanicalcomplicationofSTEMIandhasa
highmortalityrate.Itoftenoccurs3to7daysafterinitialmyocardialinfarction.Riskfactorsforleft
ventricularruptureincludeadvancedage,femalesex,anteriormyocardialinfarction,andincomplete
reperfusionofSTEMI.Patientsmostcommonlypresentwithpericardialtamponade(dueto
hemopericardium),pulselesselectricalactivity,anddeath.Earlyrecognition,emergent
pericardiocentesis,andsubsequentsurgicalreconstructioncanimprovesurvival.
Leftventricularthrombusoccursinapproximately10%to20%ofpatientsafteranteriormyocardial
infarctiondespitereperfusionandaggressivetreatment.Transthoracicechocardiographyisthemost
commondiagnosticmodality,andthrombusisdetectedasanechodensestructure,oftenattheapex
oftheleftventricle(Figure9).Treatmentinvolvestheuseoftherapeuticwarfarinfor3to6months
followingmyocardialinfarctiontoreducetheriskofstrokeorsystemicembolization.

KeyPoints
InpatientswithSTelevationmyocardialinfarction,whenpercutaneouscoronaryintervention
cannotbereadilyachievedwithin120minutes,thrombolytictherapyisrecommendedinthe
absenceofcontraindications.
PatientswithSTelevationmyocardialinfarctionwhoreceivethrombolytictherapyshouldbe
transferredtoapercutaneouscoronaryinterventioncapablefacilitybecauseofthepotentialfor
thrombolyticfailure.

NonSTElevationAcuteCoronarySyndromes
ThemostcommonpathophysiologyofNSTEACSisnonocclusivecoronaryatherosclerosiswithor
withoutthrombusformation.ThetreatmentofUAandNSTEMIpatientsisfocusedonimprovement
inepicardialbloodflowwithmedicationsandrevascularization.Becausethelinkbetween
revascularizationandclinicaloutcomesislessclearthaninSTEMIpatients,NSTEACSpatients
shouldundergoriskstratificationpriortoinvasivetreatment.
RiskStratification
RelatedQuestion
Question111

TheTIMIriskscoreisthemostcommonlyusedtoolforestimatingtheshorttermriskfordeathand
nonfatalmyocardialinfarctioninpatientswithaNSTEACS(Table13).TheTIMIriskscoreismost
usefultoassistindecidingwhetherpatientswillbenefitfromanearlyinvasivetreatmentstrategy
(Figure10).Theestimatedratesofdeathandnonfatalmyocardialinfarctionalsoareusefultocounsel
patientsregardingtheirrisk.Inpatientsatlowrisk(TIMIscoreof02),practiceguidelines
recommendanischemiaguidedstrategythatutilizesinvasivetreatmentonlyifmedicaltherapyis
ineffective.Patientsathigherrisk(TIMIscore3)aremorelikelytobenefitfromanearlyinvasive
approach.
MedicalTherapy
RelatedQuestions
Question53
Question73
Allpatientswhopresentwithischemicchestpainshouldbetreatedinitiallywithaspirin,blockers,
andnitrates.However,comparedwithSTEMI,inwhichreperfusionistheprimarygoaloftherapy,
oncethediagnosisofUAorNSTEMIhasbeenestablished(throughtheECGandbiomarkers),risk
stratificationcanbeusedtoguidetheclinicaluseofadditionaltherapies(Table14).AllNSTEACS
patientsshouldreceiveastatinandaP2Y12inhibitor(suchasclopidogrel).Inpatientsatintermediate
orhighrisk(TIMIscore3),additionaltherapies,suchasanticoagulantagentsoraglycoprotein
IIb/IIIainhibitor,shouldbeconsidered.
AntiplateletMedications

RelatedQuestions
Question44
Question101
Theinitialaspirindoseshouldbe325mgatthetimeofpresentationforischemicchestpain.Patients
whoareallergictoaspirinshouldbeadministeredclopidogrelatthetimeofpresentation.Although
thereremainsdebateaboutsubsequentaspirindosingbasedonpatientriskandwhether
revascularizationwithPCIorCABGoccurs,mostpatientscanbetreatedwithadoseof81mgdaily
indefinitely(especiallywhendualantiplatelettherapyisbeingused).
Dualantiplatelettherapy(aspirinplusclopidogrel,prasugrel,orticagrelor)isrecommendedinall
patientswithNSTEACS,regardlessofTIMIriskscore,unlessanincreasedriskofbleedingexists
(seeTable9).Theuseofclopidogrel,inadditiontoaspirin,isthebeststudiedcombination.
Clopidogrelshouldbegivenasaloadingdose(300mgor600mg)athospitaladmissionand
administeredasa75mgdailydoseforatleast1yearregardlessoftheneedforPCIorCABG.
Patientswithabaremetalstentwhocannottoleratedualantiplatelettherapyforthefullyear(for
example,becauseofbleeding,needforsurgery,orproblemswithadherence)shouldremainonthe
therapyforatleast4weeks.IfCABGisultimatelyrequired,clopidogrelshouldbediscontinuedand
CABGshouldbepostponedfor5to7daysinordertoavoidperioperativebleeding.
TwooralP2Y12inhibitors,prasugrelandticagrelor,havebeendeveloped,andwhentested,were
superiortoclopidogrelinUAandNSTEMIpatients.Ticagrelorandprasugreldonotrequirehepatic
metabolism,aremorepotent,andhaveafasteronsetofactionwhencomparedwithclopidogrel.
Theseagentsalsoshouldbediscontinued5to7daysormorepriortoCABG.
AdministrationofglycoproteinIIb/IIIainhibitorsinpatientswithNSTEACSdoesnotappeartobeof

netclinicalbenefitunlesshighriskfeatures,suchasongoinganginaorevidenceofischemiaafterthe
initiationofstandardantiplateletandantianginalmedications,reinfarction,orheartfailure,are
present.However,theseagents,incombinationwithUFHorbivalirudin,areindicatedatthetimeof
PCIinpatientswithNSTEACSwhoultimatelyrequirerevascularization.Becauseoftheirpotent
antiplateletactivity,themainadverseeffectofglycoproteinIIb/IIIainhibitorsisincreasedriskof
majorandminorbleedingevents.
AnticoagulantMedications

Theuseofanticoagulantmedications(UFH,LMWH,fondaparinux,andbivalirudin)hasbeena
cornerstoneoftherapyforNSTEACSsformorethanthreedecades.Thechoiceofaparticularagent
isbasedonthepatient'sbleedingrisk,TIMIriskscore,comorbidconditions(suchaschronickidney
disease),planforanearlyinvasiveversusaconservativestrategy,timingofcoronaryangiography,
andphysicianpreference.
UFHandLMWHarethemostwidelyusedanticoagulantsforNSTEACSs.Inpatientsinwhoman
earlyinvasiveapproachisplannedandinpatientswithchronickidneydisease,UFHispreferredover
LMWH.Inpatientsinwhomaconservativestrategyisplanned,bothLMWHandfondaparinuxhave
beenprovedtobesafeandeffective.AdvantagesoffondaparinuxandLMWHincludetheabilityto
doseonceortwicedailyratherthancontinuouslyandnorequirementtomonitortherapeuticlevels.
Becauseofasignificantlyincreasedbleedingrisk,theuseoftheanticoagulantbivalirudiniscurrently
notrecommendedbyclinicalguidelinesotherthanduringPCIorinpatientswhoareallergicto
heparinbasedproducts.
AntianginalMedications

Unlesscontraindicated,oralblockersshouldbeinitiatedinallpatientswhopresentwithaNSTE
ACS.Intravenousblockerscanalsobeadministeredhowever,cautionshouldbeusedinpatients
withheartfailure,advancedage,advancedatrioventricularblock,andhypotension.
NitratesthatcanbeadministeredtoNSTEACSpatientsincludeintravenous,topical,oral,and
sublingualformulations.Intravenousnitratesaretypicallyusedinpatientswithongoingchestpainor
borderlinebloodpressureorhemodynamics.Inpatientswithoutactivesymptoms,topicalandoral
formulationsshouldbeprescribedinordertopreventrecurrentsymptoms.Sublingualnitroglycerinis
oftenprescribedonanasneededbasisforneworworseningangina.Allformsofnitratesshouldbe
avoidedinpatientswhohavetakenaPDE5inhibitor(suchassildenafilorvardenafil)within24
hours.
Calciumchannelblockersandranolazinedonothaveclearindicationsforuseinpatientspresenting
withanACS.Opioids,suchasmorphine,maybeadministeredforsymptomaticreliefofpatientswith
ongoingchestpain,althoughcautionisadvisedbecauseoftheirbloodpressureloweringeffects.
LipidLoweringMedications

ThebenefitsofstatintherapyinACSpatientsarewellestablishedhowever,thetimingofinitiation
(hospitaladmissionversusatthetimeofPCIversushospitaldischarge)islessclear.Recentstudies
suggestthathighintensitydosingofatorvastatinorrosuvastatinisassociatedwithimproved2year
survivalafterACS.Currenttreatmentguidelinesrecommendtheinitiationofahighintensitystatinin
patientsatveryhighcardiovascularrisk,includingthosepatientswithanACS.
InvasiveVersusIschemiaGuidedTreatment
Oncemedicaltherapyhasbeeninitiatedandriskstratificationhasoccurred,guidelinesrecommend

thatpatientswithalowriskNSTEACSbetreatedconservativelywithanischemiaguidedstrategy
andthatintermediatetohighriskpatientsbeconsideredforearlyinvasivetreatment.Patientstreated
withanischemiaguidedstrategyshouldundergononinvasivestresstestingbeforehospitaldischarge
coronaryangiographyandsubsequentPCIorCABGshouldbereservedforthosewithrecurrent
symptomsorhighriskfeaturesonstresstesting.Highriskpatientsassignedtoanearlyinvasive
strategy(coronaryangiographyandsubsequentPCIorCABGwithin24hoursofinitial
hospitalization)havebeenshowntohaveimprovedoutcomeswhencomparedwithhighriskpatients
treatedconservatively.Forpatientswhoareappropriateforanearlyinvasivestrategy,thereisno
evidencethatveryearlyangiography(<6hoursorathospitaladmission)offersincrementalbenefit.
ClinicalguidelinesrecommendtheuseofearlyinvasivetreatmentinNSTEACSpatientsregardless
ofriskstratificationwhohaverecurrentsymptoms,hemodynamicinstability,orelectricalinstability.
CABGisoftenrecommendedforACSpatientswithspecificangiographiccriteria(thatis,leftmain
diseaseandmultivesselCADwithorwithoutproximalleftanteriordescendingstenosis)with
concomitantleftventricularsystolicdysfunctionand/ordiabetesmellitus.

KeyPoints
Allpatientswhopresentwithischemicchestpainshouldbetreatedinitiallywithaspirin,
blockers,andnitratesoncethediagnosisofanonSTelevationacutecoronarysyndromehas
beenestablished,riskstratificationcanbeusedtoguidetheclinicaluseofadditionaltherapies.
AllpatientswithanonSTelevationacutecoronarysyndromeshouldreceiveastatinanddual
antiplatelettherapywithaspirinandaP2Y12inhibitorinpatientsatintermediateorhighrisk,
additionaltherapies(anticoagulantagents,glycoproteinIIb/IIIainhibitor)shouldbeconsidered.
Dualantiplatelettherapyisrecommendedforatleast1yearinallpatientswithanonST
elevationacutecoronarysyndrome,unlessanincreasedriskofbleedingexists.
Oncemedicaltherapyhasbeeninitiatedandriskstratificationhasoccurred,guidelines
recommendthatlowriskpatientswithanonSTelevationacutecoronarysyndromebetreated
conservativelyandthatintermediatetohighriskpatientsbeconsideredforearlyinvasive
treatment.

AcuteCoronarySyndromesNotAssociatedwithObstructiveCoronaryDisease
RelatedQuestion
Question21
Althoughplaqueruptureatthesiteofatheroscleroticplaquedepositionisthemostcommoncauseof
ACS,otherdiseaseentitiesmaycausepatientstopresentwithchestpain,transientECGchanges,and
elevatedcardiacbiomarkers.Thediagnosisofthesediseasesisgenerallymadeoncediagnostic
coronaryangiographyhasconfirmedtheabsenceofobstructivecoronarystenoses.
Coronaryvasospasmoftenoccursinnormalornearnormalcoronaryarteries,andspasmcanbe
triggeredbytheuseofillicitdrugs,suchascocaineormethamphetamine.Inpatientswhopresent
withischemicchestpainatrestandtransientSTsegmentelevationordepression,thediagnosisof
vasospasmisoftenoneofexclusiononceangiographyconfirmstheabsenceofobstructiveCAD.
Vasospasmismostfrequentlytreatedwithlongtermnitratesandcalciumchannelblockersand
avoidanceoftriggerssuchasillicitdrugs.
Takotsubocardiomyopathy,oftentemporallyassociatedwithastressfulevent,canmimicanACS
withthepresenceofchestpain,ECGchanges,andelevatedcardiacbiomarkers(seeHeartFailure).
However,coronaryangiographyisusuallynormalorshowsonlyminimalatheroscleroticdisease,and

leftventriculographyisclassicallydefinedbythepresenceofmidwallandapicalwallmotion
abnormalitieswithsparingofthebasalsegments.Treatmentissupportive,andmorethan95%of
patientshaveresolutionofsymptomsandrecoveryofleftventricularfunctionwithin7days.
Owingtotheimprovedsensitivityoftroponinassays,othersystemicdiseases(suchaschronickidney
disease,sepsis,andrhabdomyolysis)andcardiacconditions(suchasheartfailure,atrialfibrillation,
andmyocarditis)canleadtoadiagnosisofACSwithoutobstructivecoronaryarterystenosison
coronaryangiography.Inmostcases,theetiologyofACSispresumedtobedemandischemia
(myocardialoxygendemandsurpassesoxygensupply)itistermedsecondarymyocardialinfarction
whencardiacbiomarkersareabnormal.Managementofthesepatientstypicallyincludestreatmentof
theunderlyingconditioninadditiontomedicaltherapy(aspirin,statin)andpreventivemeasuresfor
heartdisease.

LongTermCareAfteranAcuteCoronarySyndrome
RelatedQuestion
Question110
AllpatientswhoarediagnosedwithanACSshouldcontinueaspirin(81mg/d)indefinitely.Patients
treatedmedicallywithoutPCIshouldreceiveanoralP2Y12inhibitorforupto12months.The
optimaldurationofdualantiplatelettherapyinpatientswithanACSwhoundergoPCIwithdrug
elutingstentimplantationisatleast12months(seeTable9).InpatientswhoundergoPCIwithbare
metalstentimplantation,thedurationofdualantiplatelettherapyisatleast4weeksbutupto12
monthsastolerated.Intheabsenceofcontraindications,ACEinhibitorsandstatinsshouldbe
continuedindefinitelyinallpatientswithanACS.Thereisevidenceofbenefitfortreatmentwitha
blockerforatleast3yearsfollowinganACS,althoughmanyclinicianschoosetocontinuethese
medicationsindefinitelyiftheyarewelltolerated.
Currentguidelinesrecommendthatpatientswhoareenteringcardiacrehabilitationprogramsafter
ACSshouldundergoroutineexerciseECGtesting.Routinestresstestingisnotcurrently
recommendedforasymptomaticpatientswhoarenotenteringacardiacrehabilitationprogram.For
patientswithanACSwhoaresymptomaticafterhospitaldischarge,theuseofstresstestingis
acceptableandshouldbedeterminedbythepatient'ssymptoms(forexample,unstableangina,stable
angina),abilitytoexercise,andinterpretabilityofECG.

KeyPoint
Routinestresstestingisnotcurrentlyrecommendedforasymptomaticpatientsfollowingan
acutecoronarysyndromewhoarenotenteringacardiacrehabilitationprogram.

ManagementofCoronaryArteryDiseaseinWomen
ClinicalPresentation
Womentypicallydevelopischemicheartdiseaseatalaterageinlifethanmen.Unlikemen,women
presentmorefrequentlywithstableanginapectorisratherthananACSorsuddencardiacdeath.More
than50%ofwomenwhopresentwithtypicalanginaarediagnosedwithnonobstructivecoronary
stenoses,andthepresenceofmicrovasculardiseaseisthoughttobesignificantlyhigherinwomen
thaninmen.
Inwomenpresentingwithacutemyocardialinfarction,chestpainremainsthepredominantsymptom

however,thelikelihoodofatypicalsymptoms,suchasfatigue,dyspnea,nausea,andabdominal
complaints,issignificantlyhigherthaninmen.Inwomenwithoutsignificantobstructiononinvasive
angiography,microvasculardysfunction(eitherendotheliumdependentorendotheliumindependent)
isthoughttobethecauseofsymptoms.

EvaluationandTreatment
RelatedQuestion
Question87
Thesensitivityandspecificityofnoninvasivestresstestingfortheevaluationofchestpainarelower
inwomenthaninmen.STsegmentdeviationislessaccurateinwomenthaninmen.Clinical
guidelinesreportanimproveddiagnostictestaccuracywiththeuseofstresstestingwithimaging(see
DiagnosticTestinginCardiology).However,nospecificdiagnosticevaluationguidelinesexistfor
women,andthesameguidelinesapplytomenandwomen.
IntheCOURAGEtrial,womenwithstableanginapectorishadreducedoverallmortalityornonfatal
myocardialinfarctionwithrevascularizationtherapyascomparedwithmen.However,womenhavea
highercomplicationrate,particularlybleedingandvascularcomplications,surrounding
revascularizationprocedures.Forthesereasons,itisrecommendedthatguidelinedirectedmedical
therapybeinitiatedinwomenpriortoconsiderationforrevascularization.InwomenundergoingPCI,
atrendtowardfewersuchcomplicationshasbeenfoundwiththeuseofradialratherthanfemoral
arterialaccess.Overall,treatmentguidelinesdonotcurrentlydifferbetweenmenandwomen.Theuse
ofestrogenisnotrecommendedtoreducetheoccurrenceoffuturecardiovasculareventsinpost
menopausalwomen.

KeyPoints
Inwomenpresentingwithacutemyocardialinfarction,chestpainremainsthepredominant
symptomhowever,atypicalsymptoms,suchasfatigue,dyspnea,nausea,andabdominal
complaints,aremorelikelythaninmen.
Inwomenwithcoronaryarterydisease,itisrecommendedthatguidelinedirectedmedical
therapybeinitiatedpriortoconsiderationforrevascularizationotherwise,treatmentguidelines
donotcurrentlydifferbetweenmenandwomen.

ManagementofCoronaryArteryDiseaseinPatientswith
DiabetesMellitus
RiskandEvaluation
PatientswithdiabetesmellitusareatincreasedriskofdevelopingCAD,andcardiovascularmortality
issignificantlyhigherinthispopulation.Additionally,patientswithdiabetesmellitusoftendonot
experienceclassicanginapectorisandcanpresentwithatypicalcardiacsymptoms,suchasdyspnea,
nausea,orhyperglycemicsymptoms.Suddencardiacdeathoccurssignificantlymorefrequentlyin
personswithdiabetescomparedwiththosewithoutthedisease.Thediagnosticaccuracyof
noninvasivestresstestinginsymptomaticpatientswithdiabetesissimilartothatinpatientswithout
diabeteshowever,theassessmentofCADinasymptomaticpersonswithdiabetesiscontroversial.
Currently,theAmericanHeartAssociationrecommendsstresstestinginpatientswithdiabeteswho
are(1)symptomatic,(2)initiatinganexerciseprogram,or(3)knowntohaveCADandhavenothada
recent(>2years)stresstest.

InvasiveTreatment
Inpatientswithdiabeteswhoarecandidatesforrevascularization,thedecisiontopursuePCIor
CABGremainscontroversialanddependsonamultitudeoffactors,includingseverityandextentof
CAD,thepresenceofcomorbidconditions,andthedegreeofatheroscleroticnarrowingofsmall,
distalvessels.MultiplestudieshaveanalyzedoutcomesofpatientswithdiabetesundergoingPCIor
CABG.AlthoughCABGisgenerallyassociatedwithfewerrepeatrevascularizationprocedures,
mortalityissimilarbetweenthetwoprocedures.WhenadecisionismadetopursuePCI,theuseofa
drugelutingstentisrecommendedtoreducetheoccurrenceoftargetvesselrevascularizationbecause
ofthemoreextensivecoronaryarterydiseaseandhigherrateofrestenosisinpatientswithdiabetes.

MedicalTherapyandSecondaryPrevention
Aggressiveriskfactorreduction,controlofplasmaglucoselevels,andmedicaltherapyareessentialin
patientswithdiabetes.InmostpatientswithdiabetesandCAD,highintensitystatintherapyand
antihypertensivetreatmentwithatargetbloodpressurebelow140/90mmHgarerecommended.
BecauseoftheprotectiverenaleffectsofACEinhibitorsandangiotensinreceptorblockersinpatients
withproteinuricnephropathy,theseagentsarepreferredoverotherantihypertensiveagents,suchas
thiazidediuretics.
CommonmedicationsusedforthetreatmentofdiabetesareofspecialconcerninpatientswithCAD.
Inametaanalysis,thiazolidinediones,specificallyrosiglitazone,hadbeenassociatedwithanelevated
riskofcardiovascularevents,especiallymyocardialischemia.However,amorerecentclinicaltrial
demonstratednoelevatedriskofmyocardialinfarctionordeathinpatientsbeingtreatedwith
rosiglitazonewhencomparedwithstandardofcarediabetesdrugs.Theuseofmetforminatthetime
ofcoronaryangiography,aftermyocardialinfarction,andinpatientswithheartfailureshouldbe
avoidedbecauseofararebutpotentiallyfatalriskoflacticacidosis.

KeyPoint
Inpatientswithdiabetes,stresstestingisrecommendedbytheAmericanHeartAssociationfor
thosewhoare(1)symptomatic,(2)initiatinganexerciseprogram,or(3)knowntohave
coronaryarterydiseaseandhavenothadarecent(>2years)stresstest.

Bibliography
AmsterdamEA,WengerNK,BrindisRG,etal2014AHA/ACCGuidelineforthe
ManagementofPatientsWithNonSTElevationAcuteCoronarySyndromes:Executive
Summary:AReportoftheAmericanCollegeofCardiology/AmericanHeartAssociationTask
ForceonPracticeGuidelines.Circulation.2014Sep23.PMID:25249586
AntithromboticTrialists'(ATT)Collaboration,BaigentC,BlackwellL,CollinsR,etal.Aspirin
intheprimaryandsecondarypreventionofvasculardisease:collaborativemetaanalysisof
individualparticipantdatafromrandomisedtrials.Lancet.2009May30373(9678):184960.
PMID:19482214
BARI2DStudyGroup,FryeRL,AugustP,BrooksMM,etal.Arandomizedtrialoftherapies
fortype2diabetesandcoronaryarterydisease.NEnglJMed.2009Jun11360(24):250315.
PMID:19502645
FarkouhME,DomanskiM,SleeperLA,etalFREEDOMTrialInvestigators.Strategiesfor
multivesselrevascularizationinpatientswithdiabetes.NEnglJMed.2012Dec
20367(25):237584.PMID:23121323
GiuglianoRP,WhiteJA,BodeC,etalEARLYACSInvestigators.Earlyversusdelayed,
provisionaleptifibatideinacutecoronarysyndromes.NEnglJMed.2009May

21360(21):217690.PMID:19332455
GulatiM,CooperDeHoffRM,McClureC,etal.Adversecardiovascularoutcomesinwomen
withnonobstructivecoronaryarterydisease:areportfromtheWomen'sIschemiaSyndrome
EvaluationStudyandtheStJamesWomenTakeHeartProject.ArchInternMed.2009May
11169(9):84350.PMID:19433695
KaulS,BolgerAF,HerringtonD,etalAmericanHeartAssociationAmericanCollegeof
CardiologyFoundation.Thiazolidinedionedrugsandcardiovascularrisks:ascienceadvisory
fromtheAmericanHeartAssociationandtheAmericanCollegeofCardiologyFoundation.J
AmCollCardiol.2010Apr2755(17):188594.PMID:20413044
MehtaSR,GrangerCB,BodenWE,etalTIMACSInvestigators.Earlyversusdelayed
invasiveinterventioninacutecoronarysyndromes.NEnglJMed.2009May21360(21):2165
75.PMID:19458363
OGaraPT,KushnerFG,AscheimDD,etalAmericanCollegeofCardiology
Foundation/AmericanHeartAssociationTaskForceonPracticeGuidelines.2013ACCF/AHA
guidelineforthemanagementofSTelevationmyocardialinfarction:areportoftheAmerican
CollegeofCardiologyFoundation/AmericanHeartAssociationTaskForceonPractice
Guidelines.Circulation.2013Jan29127(4):e362425.Erratumin:Circulation.2013Dec
24128(25):e481.PMID:23247304
PatelMR,DehmerGJ,HirshfeldJW,etalACCF/SCAI/STS/AATS/AHA/ASNC2009
AppropriatenessCriteriaforCoronaryRevascularization:AReportoftheAmericanCollegeof
CardiologyFoundationAppropriatenessCriteriaTaskForce,SocietyforCardiovascular
AngiographyandInterventions,SocietyofThoracicSurgeons,AmericanAssociationfor
ThoracicSurgery,AmericanHeartAssociation,andtheAmericanSocietyofNuclear
Cardiology:EndorsedbytheAmericanSocietyofEchocardiography,theHeartFailureSociety
ofAmerica,andtheSocietyofCardiovascularComputedTomography.Circulation.2009Mar
10119(9):133052.Erratumin:Circulation.2009Apr21119(15):e488.PMID:19131581
QaseemA,FihnSD,WilliamsS,etalClinicalGuidelinesCommitteeoftheAmericanCollege
ofPhysicians.Diagnosisofstableischemicheartdisease:summaryofaclinicalpractice
guidelinefromtheAmericanCollegeofPhysicians/AmericanCollegeofCardiology
Foundation/AmericanHeartAssociation/AmericanAssociationforThoracic
Surgery/PreventiveCardiovascularNursesAssociation/SocietyofThoracicSurgeons.Ann
InternMed.2012Nov20157(10):72934.PMID:23165664
QaseemA,FihnSD,DallasP,etalClinicalGuidelinesCommitteeoftheAmericanCollegeof
Physicians.Managementofstableischemicheartdisease:summaryofaclinicalpractice
guidelinefromtheAmericanCollegeofPhysicians/AmericanCollegeofCardiology
Foundation/AmericanHeartAssociation/AmericanAssociationforThoracic
Surgery/PreventiveCardiovascularNursesAssociation/SocietyofThoracicSurgeons.Ann
InternMed.2012Nov20157(10):73543.PMID:23165665
SerruysPW,MoriceMC,KappeteinAP,etalSYNTAXInvestigators.Percutaneouscoronary
interventionversuscoronaryarterybypassgraftingforseverecoronaryarterydisease.NEnglJ
Med.2009Mar5360(10):96172.Erratumin:NEnglJMed.2013Feb7368(6):584PMID:
19228612
ShawLJ,BugiardiniR,MerzCN.Womenandischemicheartdisease:evolvingknowledge.J
AmCollCardiol.2009Oct2054(17):156175.PMID:19833255
SobelBE.Coronaryrevascularizationinpatientswithtype2diabetesandresultsoftheBARI
2Dtrial.CoronArteryDis.2010May21(3):18998.PMID:20308880
StoneGW,WitzenbichlerB,GuagliumiG,etalHORIZONSAMITrialInvestigators.
BivalirudinduringprimaryPCIinacutemyocardialinfarction.NEnglJMed.2008May
22358:221830.PMID:18499566
WallentinL,BeckerRC,BudajA,etalPLATOInvestigators,FreijA,ThorsenM.Ticagrelor
versusclopidogrelinpatientswithacutecoronarysyndromes.NEnglJMed.2009Sep
10361:104557.PMID:19717846
WiviottSD,BraunwaldE,McCabeCH,etalTRITONTIMI38Investigators.Prasugrelversus
clopidogrelinpatientswithacutecoronarysyndromes.NEnglJMed.2007Nov15

357(20):200115.PMID:17982182
Next:HeartFailure
Notes
Chapter03
0Notes
CoronaryArteryDisease
Questions
ReferenceRanges