4/4/2015

Antithrombotictreatmentofacuteischemicstrokeandtransientischemicattack

Officialreprintfrom UpToDate
www.uptodate.com 2015UpToDate

Antithrombotictreatmentofacuteischemicstrokeandtransientischemicattack
Authors
SectionEditor
JamaryOliveiraFilho,MD,MS,PhD ScottEKasner,MD
WalterJKoroshetz,MD

DeputyEditor
JohnFDashe,MD,PhD

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Mar2015.|Thistopiclastupdated:Oct16,2013.
INTRODUCTIONThemanagementofpatientswithacuteischemicstrokeinvolvesseveralphases(see"Initial
assessmentandmanagementofacutestroke").Thegoalsintheinitialphaseinclude:
Insuringmedicalstability
Determiningeligibilityforthrombolytictherapy(table1)
Movingtowarduncoveringthepathophysiologicbasisofthestroke
Timelyrestorationofbloodflowusingthrombolytictherapyisthemosteffectivemaneuverforsalvagingischemic
braintissuethatisnotalreadyinfarcted.Thereisanarrowwindowduringwhichthiscanbeaccomplished,thatis,
within4.5hoursofsymptomonset.Recommendationsforpatientsabletoreceivethrombolytictherapyarefound
elsewhere.(See"Intravenousfibrinolytic(thrombolytic)therapyinacuteischemicstroke:Therapeuticuse"and
"Reperfusiontherapyforacuteischemicstroke".)
Inadditiontothrombolysis,therearetwomajorclassesofantithromboticdrugsthatcanbeusedtotreatacute
ischemicstroke:
Antiplatelets
Anticoagulants
Thistopicwillreviewtheuseofacuteantithrombotictreatments(antiplateletagents,heparin,andlowmolecular
weightheparin)forpatientswhoarenottreatedwiththrombolytictherapy.Themanagementofspecificsubtypesof
ischemicstrokebeyondtheacutephaseisdiscussedseparately.(See"Secondarypreventionforspecificcauses
ofischemicstrokeandtransientischemicattack".)
ANTIPLATELETAGENTSInlargerandomizedcontrolledtrials,early(within48hours)initiationofaspirinhas
shownbenefitforthetreatmentofacuteischemicstroke.Inaddition,early(within24hours)initiationandshortterm
useofdualantiplatelettherapywithclopidogrelplusaspirinappearstobebeneficialforAsianpatientswithhighrisk
TIAorminorstroke.Theutilityofotherantiplateletagents,aloneorincombinationwithaspirin,remainstobe
proveninthissetting.
Theuseofantiplateletagentsforthesecondarypreventionofischemicstrokeisdiscussedindetailseparately.
(See"Antiplatelettherapyforsecondarypreventionofstroke".)
AspirinTwomajorclinicaltrialsstudiedthebenefitsandrisksofaspirininthesettingofacuteischemicstroke.
TheInternationalStrokeTrial(IST)enrolled19,435patientswithsuspectedacuteischemicstroke[1].
Patientsallocatedtoaspirin(300mg)within48hoursofsymptomonsetexperiencedsignificantreductionsin
the14dayrecurrenceofischemicstroke(2.8versus3.9percent)andinthecombinedoutcomeofnonfatal
strokeordeath(11.3versus12.4percent).
IntheChineseAcuteStrokeTrial(CAST),21,100patientswererandomizedto160mgofaspirindailyor
placebo,alsowithin48hoursoftheonsetofacuteischemicstroke[2].Aspirinallocatedpatientsexperienced
a14percentreductionintotalmortalityatfourweeks(3.3versus3.9percent).

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Takentogether,theISTandCASTtrialsdemonstratedthataspirintherapyinacuteischemicstrokeledtoa
reductionof11nonfatalstrokesordeathsper1000patientsinthefirstfewweeksbutcausedapproximatelytwo
hemorrhagicstrokes[3].Thus,approximatelyninenonfatalstrokesordeathswereavoidedforevery1000early
treatedpatients.Theseeffectsweresimilarinthepresenceorabsenceofatrialfibrillation.Usingtheendpointof
deathorresidualimpairmentleavingthepatientdependent,thecombineddatademonstratedareductionof13per
1000patientsafterseveralweekstosixmonthsoffollowup.
Asystematicreviewofantiplatelettherapyforacutestrokeincluded12trialsinvolving43,041patients,buttheIST
andCASTstudiescontributed94percentofthedata[4].Thereviewersconcludedthatstartingaspirin(160to300
mgdaily)within48hoursofpresumedischemicstrokeonsetreducedtheriskofearlyrecurrentischemicstroke
withoutamajorriskofearlyhemorrhagiccomplicationsandimprovedlongtermoutcome.
CombinationantiplateletsEarlyinitiationandshorttermuseofcombinationantiplateletagentsforacute
ischemicstrokeorTIAmaybebeneficial,buttheavailableevidenceisnotentirelyconsistent,andislimitedwith
regardtothepopulationsstudied:
TheCHANCEtrialrandomlyassigned5170Chinesepatientswithin24hoursofonsetofhighriskTIAorminor
ischemicstroketoeitherdualantiplatelettherapywithclopidogrelandaspirin(clopidogrel300mgloading
dose,then75mgdailyfor90days,plusaspirin75mgdailyforthefirst21days)ortoplaceboandaspirin(75
mgdailyfor90days)[5].Ondayone,allsubjectsinbothgroupsreceivedaspirinatadoseof75to300mg
determinedbytheclinician.At90days,therewasasignificantreductioninallstrokefortheclopidogrelplus
aspiringroupcomparedwiththeplaceboplusaspiringroup(8.2versus11.7percent,absoluteriskreduction
3.5percent,hazardratio0.68,95%CI0.570.81).Therateofhemorrhagicstrokewaslowinbothtreatment
groups(0.3percentineach).
NotethattheresultsoftheCHANCEtrialarenotgeneralizabletoallpatientswithacutestrokeorTIA,since
theinclusioncriteriaselectedforpatientswithhighriskTIA,definedasanABCD2(forAge,Bloodpressure,
Clinicalfeatures,Durationofsymptoms,andDiabetes)scoreof4(see"Initialevaluationandmanagementof
transientischemicattackandminorstroke",sectionon'ABCD2score'),andexcludedthosewithisolated
sensorysymptoms,isolatedvisualchanges,orisolateddizzinessorvertigo,andnoevidenceofacute
infarctiononneuroimaging[5].Theinclusioncriteriaalsoselectedforpatientswithminorstroke,definedasan
NIHSSscoreof3(see"Useandutilityofstrokescalesandgradingsystems",sectionon'NationalInstitutes
ofHealthStrokeScale').Furthermore,theChinesepopulationhasarelativelyhighrateoflargeartery
intracranialatheroscleroticdiseasecomparedwithCaucasians(see"Intracraniallargearteryatherosclerosis",
sectionon'Epidemiology').Thus,theCHANCEtrialresultsmaynotapplytononAsianpatientsortopatients
withlowriskTIA,andparticularlymaynotapplytopatientswithmoderateorsevereacuteischemicstroke,
whoarelikelytobeathigherriskforhemorrhagictransformationwithdualantiplatelettherapy.
TheopenlabelEARLYtrialrandomlyassigned539patientswithin24hoursofsymptomonsettotreatment
witheitherthecombinationofaspirinextendedreleasedipyridamole(aspirin25mgandextendedrelease200
mgtwicedaily)oraspirin(100mgdaily)alone[6].Aftersevendays,allpatientsreceivedopenlabelaspirin
extendedreleasedipyridamole.At90days,therewasnosignificantdifferencebetweenthetreatmentgroups
intheprimaryendpointofgoodneurologicoutcome,definedasamodifiedRankinscalescoreof0to1
assessedbytelephone(56versus52percent).Inaddition,therewasnosignificantdifferenceinthecombined
endpointofvascularadverseeventsormortality(10versus15percent).
ThestrengthoftheEARLYstudyislimitedbymethodologicissues(theopenlabeldesign,telephone
assessment)andsmallpatientnumberscomparedwiththeISTandCASTtrialsdiscussedabove.
TheFASTERtrialrandomlyassigned392patientswithin24hoursofsymptomonsettoeitheraspirinplus
clopidogrel(300mgloadingdose,then75mgdaily)oraspirinalone[7].Inaddition,patientswereseparately
allocatedtoreceiveeithersimvastatinorplacebo.Thetrialendedprematurelyduetoslowrecruitment.At90
days,therewasnosignificantdifferencebetweentreatmentgroups(aspirinplusclopidogrelversusaspirin
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alone)fortheprimaryoutcomemeasureofcombinedischemicandhemorrhagicstroke(7.1versus10.8
percent).
SinceFASTERenrolledmostlypatientswithmildstrokeorTIA[7],thesafetyresultsofFASTERwithrespect
tohemorrhagictransformationmaynotapplytothegeneralischemicstrokepopulation.Themuchlarger
MATCHtrial,withover7500patients,foundthatthecombineduseofaspirinandclopidogreldidnotoffer
greaterbenefitforstrokepreventionthaneitheragentalonebutdidsubstantiallyincreasetheriskofbleeding
complications[8].(See"Antiplatelettherapyforsecondarypreventionofstroke",sectionon'Aspirinplus
clopidogrel'.)
A2013metaanalysisofearlydualantiplatelettherapyversusmonotherapyforpatientswithnoncardioembolic
acuteischemicstrokeorTIAidentified14trialswithover9000adults[9].Themetaanalysisincludedpatients
fromtheCHANCE,EARLY,andFASTERtrials,whowereallenrolledwithin24hoursofonset,andthose
patientsfromsecondarypreventiontrialswhowereenrolledwithin72hoursofsymptomonset.Treatments
involvedseveraldifferentcombinationsofdualantiplatelettherapy(aspirinplusclopidogrel,aspirinplus
dipyridamole,aspirinpluscilostazol)andthreedifferentmonotherapyregimens(aspirin,clopidogrel,and
dipyridamole).Comparedwithmonotherapy,dualantiplatelettherapywasassociatedwithastatistically
significantreductioninrecurrentstroke(relativerisk[RR]0.69,95%CI0.600.80)andcompositevascular
eventsanddeath(RR0.71,95%CI0.630.81)andwithanonsignificantincreaseinmajorbleeding(RR1.35,
95%CI0.702.59).Thestrengthofthesefindingsislimitedbymultipleissues,includingvariabilityamong
trialsregardingpatientpopulations,antiplateletmedications,andlengthoffollowup,theinclusionofpatient
subgroupsthatenrolledearlyinsecondarypreventiontrials,theopenlabeldesignofsevenoftheincluded
trials,thelackofintentiontotreatanalysisoffivetrials,andsmalleventnumbersforcertainoutcomessuch
asintracerebralhemorrhageanddeath.
Evidencefromongoingrandomizedcontrolledtrials(eg,POINTandTARDIS[10,11])isawaitedtoconfirmwhether
combinationantiplateletregimensaresafeandsuperiortoaspirinfortheearlytreatmentofacuteischemicstroke
andTIAinbroadpopulations.
ChoosingearlyantiplatelettherapyAlthoughaspirin,clopidogrel,andthecombinationofaspirinextended
releasedipyridamoleareallacceptableoptionsforsecondarystrokeprevention,aspirinistheonlyantiplatelet
agentthathasbeenestablishedaseffectivefortheveryearlytreatmentofacuteischemicstroke(see'Aspirin'
above).Clopidogrelorticlopidinearealternativesforpatientsintoleranttoaspirin,althoughtheeffectivenessofthese
antiplateletsinacutestrokeisnotestablished.Theuseofdualantiplatelettherapyremainslargelyunproven,with
theexceptionthatshorttermtreatmentwithclopidogrelplusaspirinappearstobebeneficialforhighriskTIAand
minorstrokeinAsianpopulations(see'Combinationantiplatelets'above).
Werecommendearlyaspirintherapy(160to325mg/day)ratherthannoaspirintherapyorearly
anticoagulationformostpatientswithacuteischemicstroke.Thisrecommendationisinaccordwithcurrent
guidelinesissuedbytheAmericanCollegeofChestPhysicians[12],theAmericanHeart
Association/AmericanStrokeAssociation[13],andtheNationalInstituteforHealthandClinicalExcellence
[14].
Werecommendearlydualantiplatelettreatmentwithclopidogrelplusaspirinfor21days,followedby
clopidogrelmonotherapythroughatleastday90,forAsianpatientswithhighriskTIA(ie,ABCD2scoreof4)
orminorstroke(NIHSSscore3)(see'Combinationantiplatelets'above)[5].
BeyondtheacutephaseofischemicstrokeandTIA,longtermantiplatelettherapyforsecondarystroke
preventionshouldbecontinuedwithaspirin,clopidogrel,orthecombinationofaspirinextendedrelease
dipyridamole.(See"Antiplatelettherapyforsecondarypreventionofstroke".)
Asdiscussedbelow(see'Roleofearlyanticoagulation'below),wesuggestearlyparenteralanticoagulationrather
thanaspirinonlyforselectpatientswithacutecardioembolicischemicstrokeorTIAwhohaveintracardiac
thrombus.TheuseofantiplateletandanticoagulanttherapyforpatientswithacutestrokeorTIAcausedby
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cervicocephalicarterydissectionisreviewedelsewhere.(See"Spontaneouscerebralandcervicalarterydissection:
Treatmentandprognosis",sectionon'Antithrombotictherapy'.)
Antiplateletagentsshouldnotbeusedasanalternativetointravenousthrombolysisorotheracutetherapiesaimed
atimprovingoutcomesafterstroke[13].Antiplateletagentsshouldbestartedasearlyaspossibleafterthe
diagnosisofischemicstrokeisconfirmed.However,aspirinandotherantithromboticagentsshouldnotbegiven
aloneorincombinationforthefirst24hoursfollowingtreatmentwithintravenousalteplase.Aspirinandother
antiplateletagentsmaybeusedincombinationwithsubcutaneousheparinandlowmolecularweightheparinfor
deepveinthrombosisprophylaxis.(See"Medicalcomplicationsofstroke",sectionon'VTEprophylaxis'.)
Thedevelopmentofsecondaryhemorrhagictransformationofanischemicinfarctdoesnotprecludetheearlyuseof
aspirin,particularlywhenthehemorrhageispetechial(ie,scatteredandpunctate).Itisnotclearthatstopping
aspirinwillhavemuchimpactonhematomaprogressiongiventhelonglastingeffectofaspirinonplateletfunction,
evenintheraresituationofseverehemorrhagictransformationassociatedwithclinicaldeteriorationand
developmentofparenchymalhematoma(ie,largerconfluentbleedingwithinaninfarct,oftenwithmasseffect).
However,itmaybewisetodelayinitiationifaspirinhasnotyetbeenstartedinpatientswhodevelopparenchymal
hematoma.Aspirincanthenbegivenoncethepatient'sneurologicconditionbecomesstable.
PARENTERALANTICOAGULATIONTheavailableevidencesuggeststhatearlyanticoagulationwithheparinor
lowmolecularweightheparinisassociatedwithahighermortalityandworseoutcomescomparedwithaspirin
treatmentinitiatedwithin48hoursofischemicstrokeonset[15].However,asdescribedinthefollowingsections,
clinicaltrialshavenotadequatelyevaluatedadjusteddoseintravenousanticoagulationinpatientswithselected
strokesubtypes,andonlyonetrialhasevaluatedtheroleofveryearlyanticoagulationafterstrokeonset[16].
Whileparenteralanticoagulationisnotrecommendedduringthefirst48hoursafteracuteischemicstroke,oral
anticoagulationisrecommendedforsecondarystrokepreventioninpatientswithatrialfibrillationandotherhighrisk
sourcesofcardiogenicembolism.Thetimingofitsinitiationforsuchpatientsismainlydependentonthesizeofthe
infarct,whichispresumedtocorrelatewiththeriskofhemorrhagictransformation.Thus,formedicallystable
patientswithasmallormoderatesizedinfarct,warfarincanbeinitiatedsoon(after24hours)afteradmissionwith
minimalriskoftransformationtohemorrhagicstroke,whilewithholdinganticoagulationfortwoweeksisgenerally
recommendedforthosewithlargeinfarctions,symptomatichemorrhagictransformation,orpoorlycontrolled
hypertension.(See"Strokeinpatientswithatrialfibrillation",sectionon'Timingafteracutestroke'.)
TrialsThelargestrandomizedcontrolledtrial(IST)studiedtwodosesofsubcutaneousheparininover19,000
patientswithundefinedischemicstrokeandfoundnosignificantbenefitwithheparin[1].
Asystematicreviewpublishedin2008examinedtheeffectofanticoagulanttherapyversuscontrolintheearly
treatmentofpatientswithacuteischemicstroke[17].Thisreviewincluded24trialsinvolving23,748subjectsover
80percentofthesubjectswerefromtheISTtrial.Thequalityofthetrialsvariedconsiderably.Theanticoagulants
testedwerestandardunfractionatedheparin,lowmolecularweightheparins,heparinoids,oralanticoagulants,and
thrombininhibitors.Thefollowingwerethemajorfindings:
Basedupon11trials(22,776patients),anticoagulanttherapydidnotreducetheoddsofdeathfromall
causes(oddsratio1.05,95%CI0.981.12).
Baseduponeighttrials(22,125patients),anticoagulantsdidnotreducetheoddsofbeingdeadordependent
attheendoffollowup(oddsratio0.99,95%CI0.931.04).
Althoughfullanticoagulanttherapywasassociatedwithaboutninefewerrecurrentischemicstrokesper1000
patientstreated,itwasalsoassociatedwithanineper1000increaseinsymptomaticintracranial
hemorrhages.Similarly,anticoagulantsavoidedaboutfourpulmonaryemboliper1000,butthisbenefitwas
offsetbyanextraninemajorextracranialhemorrhagesper1000.
Sensitivityanalysesdidnotidentifyaparticulartypeofanticoagulantregimenorpatientcharacteristic
associatedwithnetbenefit.
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Similarly,a2013individualpatientlevelmetaanalysisoffivetrialsthatcomparedheparins(ie,unfractionated
heparin,heparinoids,orlowmolecularweightheparin)withaspirinorplaceboforacuteischemicstrokefoundno
benefitofheparinsforsubgroupsofpatientsconsideredtohaveanincreasedriskofthromboticeventsora
decreasedriskofhemorrhagicevents[18].Again,theISTtrialprovidedover80percentoftheoutcomes.
A2002systematicreviewassessedtheeffectivenessofanticoagulantscomparedwithantiplateletagentsinacute
ischemicstroke[15].Thereviewersconcludedthatanticoagulantsoffernonetadvantagesoverantiplateletagents
andrecommendthatantiplateletagentsshouldbetheantithromboticagentsoffirstchoice.However,this
conclusionwasdriveninpartbythelackofrandomizedtrialscomparinganticoagulationwithantiplatelettherapyin
thehighrisksettingswherewebelieveanticoagulationshouldbeconsidered.
StrokesubtypesClinicaltrialshavenotadequatelyevaluatedadjustedintravenousanticoagulationinpatients
withselectedstrokesubtypes.Withthiscaveatinmind,thereareconflictingdataregardingthebenefitof
intravenousunfractionatedheparinorlowmolecularweightheparininthesubgroupofpatientswithlargevessel
atheroscleroticdisease.
TheTOASTtrialevaluatedtheefficacyofthelowmolecularweightheparinoiddanaparoidadministeredasan
intravenousboluswithin24hoursofsymptomonsetandcontinuedforsevendaysin1281patientswithacute
ischemicstroke[19].Comparedtoplacebo,danaparoidwasassociatedwithnoimprovementinoverall
outcomeatthreemonths(75and74percent).However,subgroupanalysissuggestedahigherrateof
favorableoutcomesinpatientstreatedwithdanaparoidwhohadalargearteryatheroscleroticstroke(68
versus55percentwithplacebo).Asubsequentanalysisofthisstudysuggestedthatacuteperformanceof
carotiddupleximagingtoidentifypatientswithcarotidocclusionorseverestenosismayimproveselectionof
patientswhocouldbenefitfromuseofthisagent[20].
TheFISStristrialevaluatedthelowmolecularweightheparinnadroparin(3800antifactorXainternational
units,0.4mLsubcutaneouslytwicedaily)versusaspirin(160mgoncedaily)startedwithin48hoursofacute
ischemicstrokeonsetandcontinuedfor10days[21].Themainstudypopulationwas353patientswith
confirmedlargearteryocclusivedisease,consistingof300withintracranial,11withextracranial,and42with
bothintracranialandextracranialdisease.Themeantimetotreatmentwasnearly30hours.Therewasno
significantdifferencebetweentreatmentwithnadroparinoraspirinfortheproportionofpatientswithgood
outcomeatsixmonths(73versus69percent).
Intheonlytrialofunfractionatedheparininhyperacutestroke,asinglecenterrandomlyassigned418patients
withnonlacunarhemisphericinfarction(ofcardioembolic,atherothrombotic,orunknown/undeterminedorigin)
toreceiveeitherintravenousheparinorsalinewithinthreehoursofstrokeonset[16].Treatmentcontinuedfor
fivedays.Afavorableoutcomeat90days,theprimaryendpoint,wassignificantlymorefrequentinpatients
assignedtoheparincomparedwiththoseassignedtosaline(38.9versus28.6percent).Heparinusewas
associatedwithanincreasedriskofintracranialandextracranialbleeding,butnoincreaseinmortality.
Otherstudiesofheparintherapyinacutestrokedidnotconsidertheetiologyofstrokeandyieldedmixedresults
[1,2224].
AtrialfibrillationandcardioembolicstrokeAsubjectofintensedebateistheroleofimmediate
anticoagulationwithheparininstrokepatientswithatrialfibrillation(AF).Itappearsthatearlytreatmentwithheparin
inpatientswithAFwhohaveanacutestrokecausesmoreharmthangood.(See"Strokeinpatientswithatrial
fibrillation".)
A2007metaanalysisexaminedseventrialsinvolving4624patientsandcomparedheparinorlowmolecularweight
heparinsstartedwithin48hoursforacutecardioembolicstrokewithothertreatments(aspirinorplacebo)[25].The
followingobservationswerereported:
Anticoagulantswereassociatedwithastatisticallynonsignificantreductioninrecurrentischemicstrokewithin
7to14days(3.0versus4.9percent,oddsratio[OR]0.68,95%CI0.441.06)
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Anticoagulantswereassociatedwithastatisticallysignificantincreaseinsymptomaticintracranial
hemorrhage(2.5versus0.7percent,OR2.89,95%CI1.197.01)
Anticoagulantsandothertreatmentshadasimilarrateofdeathordisabilityatfinalfollowup(approximately
74percent)
Thus,theresultsdonotsupportearlyanticoagulanttreatmentofacutecardioembolicstroke[25].
ProgressingstrokeHeparinwasoncewidelyusedtotreatpatientswhocontinuedtohaveneurologic
deteriorationinthefirsthoursordaysafterischemicstroke(ie,progressingstroke,alsoreferredtoasstrokein
evolution).TheTOASTtrialdidnotfindanimprovementinoutcomeswithdanaparoidtreatmentinsuchpatients
[19],nordidanonrandomizedstudyofheparintherapy[26].Thesefindingsdonotsupportaroleforheparinin
haltingneurologicworseningafterstroke.
RoleofearlyanticoagulationGuidelinesissuedin2013bytheAmericanHeartAssociation/AmericanStroke
Associationstatethaturgentanticoagulationisnotrecommendedforthetreatmentofpatientswithacuteischemic
stroke[13].Similarly,2012guidelinesfromtheAmericanCollegeofChestPhysicians(ACCP)recommendearly
aspirintherapyovertherapeuticparenteralanticoagulationforpatientswithacuteischemicstrokeorTIA[12].
Whilemanyspecialistsbelieveithasnoroleatallintheearlyacutephaseofischemicstroke,someexpertshave
usedearlyanticoagulationforvariousischemicstrokesubtypes,includingcardioembolicstrokeduetoatrial
fibrillationandstrokeduetolargearterystenosesorarterialdissection.However,the2012ACCPguidelinesnote
thatareviewoftheliteraturedoesnotsupporttheuseofanticoagulationinthesesubgroups[12].Othersubgroups
atparticularlyhighriskforrecurrentembolism,suchaspatientswithmechanicalheartvalvesorintracardiac
thrombus,wereeithernotincludedorwereunderrepresentedintrialsofacuteantithrombotictherapyforstroke.The
ACCPnotesthattheoptimalchoiceofacuteantithrombotictherapyinthesepatientsisuncertain[12].
Inagreementwiththenationalguidelines,werecommendnotusingfulldoseparenteralanticoagulationfor
treatmentofunselectedpatientswithacuteischemicstrokebecauseoflimitedefficacyandanincreasedriskof
bleedingcomplications.Instead,werecommendearlyaspirintherapy(160to325mg/day)formostpatientswith
acuteischemicstrokeorTIA.(See'Aspirin'aboveand'Choosingearlyantiplatelettherapy'above.)
Althoughbenefitisunproven,wesuggestearlyparenteralanticoagulationratherthanaspirinforselectpatientswith
acutecardioembolicischemicstrokeorTIAwhohaveintracardiacthrombusassociatedwithmechanicalornative
heartvalves.Werecognizethatthisapproachiscontroversialsomeexpertsfavortreatmentwithaspirinratherthan
anticoagulationinthissettingforpatientswithanacutebraininfarction.Oursuggestiontouseearlyparenteral
anticoagulationfortheseselectedpatientsappliesonlytothosewithasmallbraininfarctorTIAandnoevidenceof
hemorrhageonbrainimaging.Anticoagulationshouldnotbegivenforthefirst24hoursfollowingtreatmentwith
intravenousalteplase.
TheuseofantithrombotictherapyforischemicstrokeandTIAcausedbycervicalarterydissectionisdiscussed
elsewhere.(See"Spontaneouscerebralandcervicalarterydissection:Treatmentandprognosis",sectionon
'Antithrombotictherapy'.)
Fulldoseanticoagulationshouldnotbeusedforpatientswithalargeinfarction(baseduponclinicalsyndromeor
brainimagingfindings),uncontrolledhypertension,orotherbleedingconditions.(See'Contraindications'below.)
AdministrationIntheselectedpatientswhoreceiveheparinintheacutestrokesetting,abolusisnot
administered.Onegrouphasproposedaweightbasednomogramforheparininfusionsthat,comparedwithusual
heparintherapy,isassociatedwithfewercomplications,fewermistakesindoseadjustment,improved
anticoagulation,anddecreasednursingandhousestafflabor(table2)[27].
Enoxaparin1mg/kgdoseevery12hours(orotherlowmolecularweightheparins)maybeusedasanalternativeto
intravenousheparininpatientswithacutestrokewhenearlyanticoagulationisdesiredtopreventrecurrentcerebral
embolismthelimitedavailableevidencesuggeststhatlowmolecularweightheparinshavesimilarefficacy,
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advantagesinadministrationandmonitoring,andreducedratesofthrombocytopeniacomparedwithheparin.
Theuseofintravenousanticoagulationforprophylaxisofdeepveinthrombosisisdiscussedseparately.(See
"Medicalcomplicationsofstroke",sectionon'VTEprophylaxis'.)
ContraindicationsAnticoagulationinthesettingofacutestrokemayonlybeconsideredafterabrainimaging
studyhasexcludedhemorrhageandestimatedthesizeoftheinfarct.Earlyanticoagulationshouldbeavoidedwhen
potentialcontraindicationstoanticoagulationarepresent,suchasalargeinfarction(baseduponclinicalsyndrome
orbrainimagingfindings),uncontrolledhypertension,orotherbleedingconditions.
Althoughthereisnostandarddefinition,manystrokeexpertsconsider"large"infarctstobethosethatinvolvemore
thanonethirdofthemiddlecerebralarteryterritoryormorethanonehalfoftheposteriorcerebralarteryterritory
baseduponneuroimagingwithCTorMRI.Infarctsizecanalsobeclinicallydefined,butthisprocesscanresultin
underestimationofthetrueinfarctvolumewhensocalled"silent"areasofassociationcortexareinvolved.
Clinicalestimationofinfarctsizemaybeimprovedbyusingvalidatedscalesthathavebeencorrelatedwithinfarct
volumeandclinicaloutcome,suchastheNationalInstitutesofHealthStrokeScale(NIHSS)(table3).Asan
example,onestudyfoundthatanNIHSSscore>15wasassociatedwithamedianinfarctvolumeof55.8cm3and
worseoutcomethanNIHSSscoresof1to7(medianvolumeof7.9cm3)or8to15(medianvolumeof31.4cm3)
[28].
Thus,patientswithanNIHSSscore>15generallyhavealargeinfarct.However,itshouldberecognizedthatpartof
theclinicaldeficitintheearlyhoursofanacutestrokemaybeattributedtothepenumbra,wherethebrainis
ischemicbutnotinfarcted.
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,TheBasicsand
BeyondtheBasics.TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgrade
readinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.These
articlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.Beyondthe
Basicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewrittenatthe
10thto12thgradereadinglevelandarebestforpatientswhowantindepthinformationandarecomfortablewith
somemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthese
topicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon
patientinfoandthekeyword(s)ofinterest.)
Basicstopics(see"Patientinformation:Stroke(TheBasics)")
BeyondtheBasicstopics(see"Patientinformation:Strokesymptomsanddiagnosis(BeyondtheBasics)"
and"Patientinformation:Ischemicstroketreatment(BeyondtheBasics)")
SUMMARYANDRECOMMENDATIONS
Althoughaspirin,clopidogrel,andthecombinationofaspirinextendedreleasedipyridamoleareallacceptable
optionsforsecondarystrokeprevention,aspirinistheonlyantiplateletagentthathasbeenestablishedas
effectivefortheearlytreatmentofacuteischemicstroke.(See'Antiplateletagents'above.)
Clinicaltrialshavenotadequatelyevaluatedtheroleofveryearly(ie,withinhoursofstrokeonset)
anticoagulationforacuteischemicstrokeorforselectedstrokesubtypes.However,theavailableevidence
suggeststhatearlyanticoagulationisassociatedwithahighermortalityandworseoutcomescomparedwith
aspirintreatmentinitiatedwithin48hoursofischemicstrokeonset.(See'Parenteralanticoagulation'above.)
FormostpatientswithacuteischemicstrokeorTIAwhoarenotreceivingoralanticoagulants,werecommend
earlyaspirintherapy(160to325mg/day)ratherthannoaspirintherapy(Grade1A)orparenteral
anticoagulationtherapy(Grade1B).Aspirinshouldbestartedasearlyaspossibleafterthediagnosisof
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ischemicstrokeisconfirmedandideallywithin48hoursofstrokeonset.However,aspirinshouldnotbegiven
forthefirst24hoursfollowingtreatmentwithintravenousorintraarterialthrombolytictherapy.(See'Aspirin'
aboveand'Choosingearlyantiplatelettherapy'above.)
ForAsianpatientswithhighriskTIA(ie,ABCD2scoreof4)orminorstroke(ie,NIHSSscore3),we
recommendearlydualantiplatelettreatment,ratherthanaspirinmonotherapy,withclopidogrel(300mg
loadingdose,then75mgdaily)plusaspirin(75to300mgloadingdose,then75to81mgdaily)for21days,
followedbyclopidogrelmonotherapy(75mgdaily)throughatleastday90(Grade1B).Treatmentshouldbe
startedwithin24hoursofsymptomonset.(See'Combinationantiplatelets'aboveand'Choosingearly
antiplatelettherapy'above.)
BeyondtheacutephaseofischemicstrokeandTIA,longtermantiplatelettherapyforsecondarystroke
preventionshouldbecontinuedwithaspirin,clopidogrel,orthecombinationofaspirinextendedrelease
dipyridamole.(See"Antiplatelettherapyforsecondarypreventionofstroke".)
Theuseofantithrombotictherapyforpatientswhohaveischemicneurologicsymptomscausedbycervicalor
intracranialarterydissectionisdiscussedseparately.(See"Spontaneouscerebralandcervicalartery
dissection:Treatmentandprognosis",sectionon'Antithrombotictherapy'.)
ForpatientswithacutecardioembolicischemicstrokeorTIAwhohaveintracardiacthrombusassociatedwith
mechanicalornativeheartvalves,wesuggestearlyparenteralanticoagulationratherthanaspirin(Grade2C).
Thisapproachiscontroversial.Otherexpertsfavorearlytreatmentwithaspirinratherthananticoagulationin
thissettingforpatientswithaninfarct.Oursuggestiontouseearlyparenteralanticoagulationforthese
selectedpatientsappliesonlytothosewithasmallbraininfarctorTIAandnoevidenceofhemorrhageon
brainimaging.(See'Roleofearlyanticoagulation'above.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
REFERENCES
1. TheInternationalStrokeTrial(IST):arandomisedtrialofaspirin,subcutaneousheparin,both,orneither
among19435patientswithacuteischaemicstroke.InternationalStrokeTrialCollaborativeGroup.Lancet
1997349:1569.
2. CAST:randomisedplacebocontrolledtrialofearlyaspirinusein20,000patientswithacuteischaemic
stroke.CAST(ChineseAcuteStrokeTrial)CollaborativeGroup.Lancet1997349:1641.
3. ChenZM,SandercockP,PanHC,etal.Indicationsforearlyaspirinuseinacuteischemicstroke:A
combinedanalysisof40000randomizedpatientsfromthechineseacutestroketrialandtheinternational
stroketrial.OnbehalfoftheCASTandISTcollaborativegroups.Stroke200031:1240.
4. SandercockPA,CounsellC,GubitzGJ,TsengMC.Antiplatelettherapyforacuteischaemicstroke.
CochraneDatabaseSystRev2008:CD000029.
5. WangY,WangY,ZhaoX,etal.Clopidogrelwithaspirininacuteminorstrokeortransientischemicattack.N
EnglJMed2013369:11.
6. DenglerR,DienerHC,SchwartzA,etal.Earlytreatmentwithaspirinplusextendedreleasedipyridamolefor
transientischaemicattackorischaemicstrokewithin24hofsymptomonset(EARLYtrial):arandomised,
openlabel,blindedendpointtrial.LancetNeurol20109:159.
7. KennedyJ,HillMD,RyckborstKJ,etal.Fastassessmentofstrokeandtransientischaemicattackto
preventearlyrecurrence(FASTER):arandomisedcontrolledpilottrial.LancetNeurol20076:961.
8. DienerHC,BogousslavskyJ,BrassLM,etal.Aspirinandclopidogrelcomparedwithclopidogrelaloneafter
recentischaemicstrokeortransientischaemicattackinhighriskpatients(MATCH):randomised,double
blind,placebocontrolledtrial.Lancet2004364:331.
9. WongKS,WangY,LengX,etal.Earlydualversusmonoantiplatelettherapyforacutenoncardioembolic
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Antithrombotictreatmentofacuteischemicstrokeandtransientischemicattack

ischemicstrokeortransientischemicattack:anupdatedsystematicreviewandmetaanalysis.Circulation
2013128:1656.
10. PlateletOrientedInhibitioninNewTIAandMinorIschemicStroke(POINT)Trial
http://clinicaltrials.gov/ct2/show/NCT00991029(AccessedonJuly02,2013).
11. TripleAntiplateletsforReducingDependencyafterIschaemicStroke(TARDIS)
http://clinicaltrials.gov/show/NCT01661322(AccessedonJuly02,2013).
12. LansbergMG,O'DonnellMJ,KhatriP,etal.Antithromboticandthrombolytictherapyforischemicstroke:
AntithromboticTherapyandPreventionofThrombosis,9thed:AmericanCollegeofChestPhysicians
EvidenceBasedClinicalPracticeGuidelines.Chest2012141:e601S.
13. JauchEC,SaverJL,AdamsHPJr,etal.Guidelinesfortheearlymanagementofpatientswithacute
ischemicstroke:aguidelineforhealthcareprofessionalsfromtheAmericanHeartAssociation/American
StrokeAssociation.Stroke201344:870.
14. NationalInstituteforHealthandClinicalExcellence.Stroke:Thediagnosisandacutemanagementofstroke
andtransientischaemicattacks.RoyalCollegeofPhysicians,London2008.http://www.nice.org.uk/CG068
(AccessedonFebruary01,2011).
15. BergeE,SandercockP.Anticoagulantsversusantiplateletagentsforacuteischaemicstroke.Cochrane
DatabaseSystRev2002:CD003242.
16. CamerlingoM,SalviP,BelloniG,etal.Intravenousheparinstartedwithinthefirst3hoursafteronsetof
symptomsasatreatmentforacutenonlacunarhemisphericcerebralinfarctions.Stroke200536:2415.
17. SandercockPA,CounsellC,KamalAK.Anticoagulantsforacuteischaemicstroke.CochraneDatabase
SystRev2008:CD000024.
18. WhiteleyWN,AdamsHPJr,BathPM,etal.Targeteduseofheparin,heparinoids,orlowmolecularweight
heparintoimproveoutcomeafteracuteischaemicstroke:anindividualpatientdatametaanalysisof
randomisedcontrolledtrials.LancetNeurol201312:539.
19. Lowmolecularweightheparinoid,ORG10172(danaparoid),andoutcomeafteracuteischemicstroke:a
randomizedcontrolledtrial.ThePublicationsCommitteefortheTrialofORG10172inAcuteStroke
Treatment(TOAST)Investigators.JAMA1998279:1265.
20. AdamsHPJr,BendixenBH,LeiraE,etal.Antithrombotictreatmentofischemicstrokeamongpatientswith
occlusionorseverestenosisoftheinternalcarotidartery:AreportoftheTrialofOrg10172inAcuteStroke
Treatment(TOAST).Neurology199953:122.
21. WongKS,ChenC,NgPW,etal.Lowmolecularweightheparincomparedwithaspirinforthetreatmentof
acuteischaemicstrokeinAsianpatientswithlargearteryocclusivedisease:arandomisedstudy.Lancet
Neurol20076:407.
22. KayR,WongKS,YuYL,etal.Lowmolecularweightheparinforthetreatmentofacuteischemicstroke.N
EnglJMed1995333:1588.
23. DienerHC,RingelsteinEB,vonKummerR,etal.Treatmentofacuteischemicstrokewiththelowmolecular
weightheparincertoparin:resultsoftheTOPAStrial.TherapyofPatientsWithAcuteStroke(TOPAS)
Investigators.Stroke200132:22.
24. BathPM,LindenstromE,BoysenG,etal.Tinzaparininacuteischaemicstroke(TAIST):arandomised
aspirincontrolledtrial.Lancet2001358:702.
25. PaciaroniM,AgnelliG,MicheliS,CasoV.Efficacyandsafetyofanticoagulanttreatmentinacute
cardioembolicstroke:ametaanalysisofrandomizedcontrolledtrials.Stroke200738:423.
26. RdnJlligA,BrittonM.Effectivenessofheparintreatmentforprogressingischaemicstroke:beforeand
afterstudy.JInternMed2000248:287.
27. TothC,VollC.Validationofaweightbasednomogramfortheuseofintravenousheparinintransient
ischemicattackorstroke.Stroke200233:670.
28. ThijsVN,LansbergMG,BeaulieuC,etal.Isearlyischemiclesionvolumeondiffusionweightedimagingan
independentpredictorofstrokeoutcome?Amultivariableanalysis.Stroke200031:2597.
Topic1082Version16.0
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GRAPHICS
Eligibilitycriteriaforthetreatmentofacuteischemicstrokewith
recombinanttissueplasminogenactivator(alteplase)
Inclusioncriteria
Clinicaldiagnosisofischemicstrokecausingmeasurableneurologicdeficit
Onsetofsymptoms<4.5hoursbeforebeginningtreatmentiftheexacttimeofstrokeonset
isnotknown,itisdefinedasthelasttimethepatientwasknowntobenormal
Age18years

Exclusioncriteria
Historical
Significantstrokeorheadtraumainthepreviousthreemonths
Previousintracranialhemorrhage
Intracranialneoplasm,arteriovenousmalformation,oraneurysm
Recentintracranialorintraspinalsurgery
Arterialpunctureatanoncompressiblesiteintheprevioussevendays
Clinical
Symptomssuggestiveofsubarachnoidhemorrhage
Persistentbloodpressureelevation(systolic185mmHgordiastolic110mmHg)
Serumglucose<50mg/dL(<2.8mmol/L)
Activeinternalbleeding
Acutebleedingdiathesis,includingbutnotlimitedtoconditionsdefinedin'Hematologic'
Hematologic
Plateletcount<100,000/mm3*
CurrentanticoagulantusewithanINR>1.7orPT>15seconds*
Heparinusewithin48hoursandanabnormallyelevatedaPTT*
CurrentuseofadirectthrombininhibitorordirectfactorXainhibitorwithevidenceof
anticoagulanteffectbylaboratorytestssuchasaPTT,INR,ECT,TT,orappropriatefactor
Xaactivityassays
HeadCTscan
Evidenceofhemorrhage
Evidenceofamultilobarinfarctionwithhypodensityinvolving>33percentofthecerebral
hemisphere

Relativeexclusioncriteria
Onlyminorandisolatedneurologicsigns
Rapidlyimprovingstrokesymptoms
Majorsurgeryorserioustraumaintheprevious14days
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Gastrointestinalorurinarytractbleedingintheprevious21days
Myocardialinfarctioninthepreviousthreemonths
Seizureattheonsetofstrokewithpostictalneurologicimpairments
Pregnancy

Additionalrelativeexclusioncriteriafortreatmentfrom3to4.5hoursfrom
symptomonset
Age>80years
OralanticoagulantuseregardlessofINR
Severestroke(NIHSSscore>25)
Combinationofbothpreviousischemicstrokeanddiabetesmellitus
aPTT:activatedpartialthromboplastintimeECT:ecarinclottingtimeINR:internationalnormalized
ratioPT:prothrombintimeNIHSS:NationalInstitutesofHealthStrokeScaleTT:thrombintime.
*Althoughitisdesirabletoknowtheresultsofthesetests,thrombolytictherapyshouldnotbe
delayedwhileresultsarependingunless(1)thereisclinicalsuspicionofableedingabnormalityor
thrombocytopenia,(2)thepatientiscurrentlyonorhasrecentlyreceivedanticoagulants(eg,
heparin,warfarin,adirectthrombininhibitor,oradirectfactorXainhibitor),(3)useof
anticoagulantsisnotknown.Forpatientswithoutrecentuseoforalanticoagulantsorheparin,
treatmentwithintravenoustPAcanbestartedbeforeavailabilityofcoagulationtestresultsbut
shouldbediscontinuediftheINR,PT,oraPTTexceedthelimitsstatedinthetable.
Theavailabledatasuggestthatundersomecircumstanceswithcarefulconsiderationand
weightingofrisktobenefitpatientsmayreceivefibrinolytictherapydespiteoneormorerelative
contraindications.Inparticular,thereisnowconsensusthatpatientswhohaveapersistent
neurologicdeficitthatispotentiallydisabling,despiteimprovementofanydegree,shouldbe
treatedwithtPAintheabsenceofothercontraindications.Anyofthefollowingshouldbe
considereddisablingdeficits:
Completehemianopsia:2onNIHSSquestion3,or
Severeaphasia:2onNIHSSquestion9,or
Visualorsensoryextinction:1onNIHSSquestion11,or
Anyweaknesslimitingsustainedeffortagainstgravity:2onNIHSSquestion5or6,or
AnydeficitsthatleadtoatotalNIHSS>5,or
Anyremainingdeficitconsideredpotentiallydisablingintheviewofthepatientandthe
treatingpractitionerusingclinicaljudgement
Adaptedfrom:
1. HackeW,KasteM,BluhmkiE,etal.Thrombolysiswithalteplase3to4.5hoursafteracute
ischemicstroke.NEnglJMed2008359:1317.
2. DelZoppoGJ,SaverJL,JauchEC,etal.Expansionofthetimewindowfortreatmentofacute
ischemicstrokewithintravenoustissueplasminogenactivator.Ascienceadvisoryfromthe
AmericanHeartAssociation/AmericanStrokeAssociation.Stroke200940:2945.
3. JauchEC,SaverJL,AdamsHPJr,etal.Guidelinesfortheearlymanagementofpatientswith
acuteischemicstroke:aguidelineforhealthcareprofessionalsfromtheAmericanHeart
Association/AmericanStrokeAssociation.Stroke201344:870.
4. ReexaminingAcuteEligibilityforThrombolysis(TREAT)TaskForce:,LevineSR,KhatriP,etal.
Review,historicalcontext,andclarificationsoftheNINDSrtPAstroketrialsexclusioncriteria:
Part1:rapidlyimprovingstrokesymptoms.Stroke201344:2500.
Graphic71462Version11.0
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Heparinadjustednomogramforstroke
Initialdosingforcontinuousintravenousheparininfusion
Weight(kg)

Initialinfusion(U/hour)

<50

500

50to59

600

60to69

700

70to79

800

80to89

900

90to99

1000

100to109

1100

110to119

1200

>119

1400

HeparinadjustmentbaseduponaPTTdrawnsixhoursafterinitiationof
therapy
aPTT(seconds)

Stopinfusion

Ratechange

RepeataPTT

<40

No

Increaseby250U/hour

6hours

40to49

No

Increaseby150U/hour

6hours

50to59

No

Increaseby100U/hour

6hours

60to90

No

Nochange

Nextmorning

91to100

No

Decreaseby100U/hour

6hours

101to120

No

Decreaseby150U/hour

6hours

>120

No

Decreaseby250U/hour

6hours

Nobolusisadministeredinpatientswithac utestroke.
Datafrom:TothC,VollC.Validationofaweightbasednomogramfortheuseofintravenousheparinin
transientischemicattackorstroke.Stroke200233:670.
Graphic53377Version2.0

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NationalInstitutesofHealthStrokeScale(NIHSS)
Administerstrokescaleitemsintheorderlisted.Recordperformanceineachcategoryafter
eachsubscaleexam.Donotgobackandchangescores.Followdirectionsprovidedforeach
examtechnique.Scoresshouldreflectwhatthepatientdoes,notwhattheclinicianthinksthe
patientcando.Theclinicianshouldrecordanswerswhileadministeringtheexamandwork
quickly.Exceptwhereindicated,thepatientshouldnotbecoached(ie,repeatedrequeststo
patienttomakeaspecialeffort).

Instructions
1a.Levelofconsciousness:The
investigatormustchoosearesponseifa
fullevaluationispreventedbysuch
obstaclesasanendotrachealtube,
languagebarrier,orotracheal
trauma/bandages.A3isscoredonlyif
thepatientmakesnomovement(other
thanreflexiveposturing)inresponseto
noxiousstimulation.

Scaledefinition

Score

0=Alertkeenlyresponsive.
1=Notalertbutarousablebyminor
stimulationtoobey,answer,orrespond.
2=Notalertrequiresrepeated
stimulationtoattend,orisobtunded
andrequiresstrongorpainful
stimulationtomakemovements(not
stereotyped).

_____

3=Respondsonlywithreflexmotoror
autonomiceffectsortotally
unresponsive,flaccid,andareflexic.
1b.LOCquestions:Thepatientisasked
themonthandhis/herage.Theanswer
mustbecorrectthereisnopartial
creditforbeingclose.Aphasicand
stuporouspatientswhodonot

0=Answersbothquestionscorrectly.
1=Answersonequestioncorrectly.
2=Answersneitherquestioncorrectly.

comprehendthequestionswillscore2.
Patientsunabletospeakbecauseof
endotrachealintubation,orotracheal
trauma,severedysarthriafromany
cause,languagebarrier,oranyother

_____

problemnotsecondarytoaphasiaare
givena1.Itisimportantthatonlythe
initialanswerbegradedandthatthe
examinernot"help"thepatientwith
verbalornonverbalcues.
1c.LOCcommands:Thepatientis
askedtoopenandclosetheeyesand
thentogripandreleasethenonparetic
hand.Substituteanotheronestep
commandifthehandscannotbeused.
Creditisgivenifanunequivocalattempt
ismadebutnotcompleteddueto
weakness.Ifthepatientdoesnot
respondtocommand,thetaskshould
bedemonstratedtohimorher

0=Performsbothtaskscorrectly.
1=Performsonetaskcorrectly.
2=Performsneithertaskcorrectly.

_____

(pantomime),andtheresultscored(ie,
followsnone,oneortwocommands).
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Patientswithtrauma,amputation,or
otherphysicalimpedimentsshouldbe
givensuitableonestepcommands.Only
thefirstattemptisscored.
2.Bestgaze:Onlyhorizontaleye
movementswillbetested.Voluntaryor
reflexive(oculocephalic)eyemovements
willbescored,butcalorictestingisnot
done.Ifthepatienthasaconjugate
deviationoftheeyesthatcanbe
overcomebyvoluntaryorreflexive
activity,thescorewillbe1.Ifapatient
hasanisolatedperipheralnerveparesis
(CNIII,IVorVI),scorea1.Gazeis
testableinallaphasicpatients.Patients
withoculartrauma,bandages,pre
existingblindness,orotherdisorderof
visualacuityorfieldsshouldbetested

0=Normal.
1=Partialgazepalsygazeis
abnormalinoneorbotheyes,butforced
deviationortotalgazeparesisisnot
present.
2=Forceddeviation,ortotalgaze
paresisnotovercomebythe
oculocephalicmaneuver.
_____

withreflexivemovements,andachoice
madebytheinvestigator.Establishing
eyecontactandthenmovingaboutthe
patientfromsidetosidewilloccasionally
clarifythepresenceofapartialgaze
palsy.
3.Visual:Visualfields(upperandlower
quadrants)aretestedbyconfrontation,
usingfingercountingorvisualthreat,as
appropriate.Patientsmaybe
encouraged,butiftheylookattheside
ofthemovingfingersappropriately,this
canbescoredasnormal.Ifthereis
unilateralblindnessorenucleation,

0=Novisualloss.
1=Partialhemianopia.
2=Completehemianopia.
3=Bilateralhemianopia(blind
includingcorticalblindness).

visualfieldsintheremainingeyeare
scored.Score1onlyifaclearcut
asymmetry,includingquadrantanopia,is
found.Ifpatientisblindfromanycause,

_____

score3.Doublesimultaneous
stimulationisperformedatthispoint.If
thereisextinction,patientreceivesa1,
andtheresultsareusedtorespondto
item11.
4.Facialpalsy:Askorusepantomime
toencouragethepatienttoshow
teethorraiseeyebrowsandcloseeyes.
Scoresymmetryofgrimaceinresponse
tonoxiousstimuliinthepoorly
responsiveornoncomprehending
patient.Iffacialtrauma/bandages,
orotrachealtube,tapeorotherphysical

0=Normalsymmetricalmovements.
1=Minorparalysis(flattened
nasolabialfold,asymmetryonsmiling).
2=Partialparalysis(totalorneartotal
paralysisoflowerface).

_____

3=Completeparalysisofoneorboth
sides(absenceoffacialmovementinthe

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barriersobscuretheface,theseshould

upperandlowerface).

beremovedtotheextentpossible.
5.Motorarm:Thelimbisplacedinthe

0=Nodriftlimbholds90(or45)

appropriateposition:extendthearms
(palmsdown)90degrees(ifsitting)or
45degrees(ifsupine).Driftisscoredif
thearmfallsbefore10seconds.The
aphasicpatientisencouragedusing

degreesforfull10seconds.

urgencyinthevoiceandpantomime,but
notnoxiousstimulation.Eachlimbis
testedinturn,beginningwiththenon
pareticarm.Onlyinthecaseof
amputationorjointfusionatthe
shoulder,theexaminershouldrecord
thescoreasuntestable(UN),andclearly
writetheexplanationforthischoice.

1=Driftlimbholds90(or45)degrees,
butdriftsdownbeforefull10seconds
doesnothitbedorothersupport.
2=Someeffortagainstgravitylimb
cannotgettoormaintain(ifcued)90(or
45)degrees,driftsdowntobed,buthas
someeffortagainstgravity.

_____

3=Noeffortagainstgravitylimbfalls.
4=Nomovement.
UN=Amputationorjointfusion,
explain:________________
5a.Leftarm
5b.Rightarm

6.Motorleg:Thelimbisplacedinthe
appropriateposition:holdthelegat30
degrees(alwaystestedsupine).Driftis
scoredifthelegfallsbefore5seconds.
Theaphasicpatientisencouragedusing
urgencyinthevoiceandpantomime,but
notnoxiousstimulation.Eachlimbis
testedinturn,beginningwiththenon
pareticleg.Onlyinthecaseof
amputationorjointfusionatthehip,the
examinershouldrecordthescoreas
untestable(UN),andclearlywritethe
explanationforthischoice.

0=Nodriftlegholds30degree
positionforfull5seconds.
1=Driftlegfallsbytheendofthe5
secondperiodbutdoesnothitbed.
2=Someeffortagainstgravityleg
fallstobedby5seconds,buthassome
effortagainstgravity.
3=Noeffortagainstgravitylegfalls

_____

tobedimmediately.
4=Nomovement.
UN=Amputationorjointfusion,
explain:________________
6a.Leftleg
6b.Rightleg

7.Limbataxia:Thisitemisaimedat
findingevidenceofaunilateral
cerebellarlesion.Testwitheyesopen.
Incaseofvisualdefect,ensuretesting

0=Absent.

isdoneinintactvisualfield.Thefinger
nosefingerandheelshintestsare
performedonbothsides,andataxiais
scoredonlyifpresentoutofproportion
toweakness.Ataxiaisabsentinthe
patientwhocannotunderstandoris

UN=Amputationorjointfusion,
explain:________________

1=Presentinonelimb.
2=Presentintwolimbs.

_____

paralyzed.Onlyinthecaseof
amputationorjointfusion,theexaminer
shouldrecordthescoreasuntestable
(UN),andclearlywritetheexplanation
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forthischoice.Incaseofblindness,test
byhavingthepatienttouchnosefrom
extendedarmposition.
8.Sensory:Sensationorgrimaceto
pinprickwhentested,orwithdrawal
fromnoxiousstimulusintheobtunded
oraphasicpatient.Onlysensoryloss
attributedtostrokeisscoredas
abnormalandtheexaminershouldtest
asmanybodyareas(arms[nothands],
legs,trunk,face)asneededto
accuratelycheckforhemisensoryloss.A
scoreof2,"severeortotalsensory
loss,"shouldonlybegivenwhena
severeortotallossofsensationcanbe
clearlydemonstrated.Stuporousand
aphasicpatientswill,therefore,probably

0=Normalnosensoryloss.
1=Mildtomoderatesensoryloss
patientfeelspinprickislesssharporis
dullontheaffectedsideorthereisa
lossofsuperficialpainwithpinprick,but
patientisawareofbeingtouched.
2=Severetototalsensoryloss
patientisnotawareofbeingtouchedin
theface,arm,andleg.
_____

score1or0.Thepatientwithbrainstem
strokewhohasbilaterallossof
sensationisscored2.Ifthepatient
doesnotrespondandisquadriplegic,
score2.Patientsinacoma(item1a=3)
areautomaticallygivena2onthisitem.
9.Bestlanguage:Agreatdealof
informationaboutcomprehensionwillbe
obtainedduringtheprecedingsections
oftheexamination.Forthisscaleitem,
thepatientisaskedtodescribewhatis
happeningintheattachedpicture,to
nametheitemsontheattachednaming
sheetandtoreadfromtheattachedlist
ofsentences.Comprehensionisjudged
fromresponseshere,aswellastoallof
thecommandsintheprecedinggeneral
neurologicalexam.Ifvisualloss
interfereswiththetests,askthepatient
toidentifyobjectsplacedinthehand,
repeat,andproducespeech.The
intubatedpatientshouldbeaskedto
write.Thepatientinacoma(item1a=3)
willautomaticallyscore3onthisitem.
Theexaminermustchooseascorefor
thepatientwithstupororlimited
cooperation,butascoreof3shouldbe
usedonlyifthepatientismuteand
followsnoonestepcommands.

10.Dysarthria:Ifpatientisthoughtto
benormal,anadequatesampleof

0=Noaphasianormal.
1=Mildtomoderateaphasiasome
obviouslossoffluencyorfacilityof
comprehension,withoutsignificant
limitationonideasexpressedorformof
expression.Reductionofspeechand/or
comprehension,however,makes
conversationaboutprovidedmaterials
difficultorimpossible.Forexample,in
conversationaboutprovidedmaterials,
examinercanidentifypictureornaming
cardcontentfrompatient'sresponse.

_____

2=Severeaphasiaallcommunication
isthroughfragmentaryexpression
greatneedforinference,questioning,
andguessingbythelistener.Rangeof
informationthatcanbeexchangedis
limitedlistenercarriesburdenof
communication.Examinercannotidentify
materialsprovidedfrompatient
response.
3=Mute,globalaphasianousable
speechorauditorycomprehension.
0=Normal.
1=Mildtomoderatedysarthria

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speechmustbeobtainedbyasking
patienttoreadorrepeatwordsfromthe
attachedlist.Ifthepatienthassevere
aphasia,theclarityofarticulationof
spontaneousspeechcanberated.Only
ifthepatientisintubatedorhasother
physicalbarrierstoproducingspeech,
theexaminershouldrecordthescoreas
untestable(UN),andclearlywritean
explanationforthischoice.Donottell

patientslursatleastsomewordsand,
atworst,canbeunderstoodwithsome
difficulty.
2=Severedysarthriapatient'sspeech
issoslurredastobeunintelligibleinthe
absenceoforoutofproportiontoany
dysphasia,orismute/anarthric.

_____

UN=Intubatedorotherphysicalbarrier,
explain:________________

thepatientwhyheorsheisbeing
tested.
11.Extinctionandinattention

0=Noabnormality.

(formerlyneglect):Sufficient
informationtoidentifyneglectmaybe
obtainedduringthepriortesting.Ifthe
patienthasaseverevisualloss
preventingvisualdoublesimultaneous
stimulation,andthecutaneousstimuli

1=Visual,tactile,auditory,spatial,or
personalinattentionorextinctionto
bilateralsimultaneousstimulationinone
ofthesensorymodalities.

arenormal,thescoreisnormal.Ifthe
patienthasaphasiabutdoesappearto
attendtobothsides,thescoreis
normal.Thepresenceofvisualspatial
neglectoranosognosiamayalsobe

2=Profoundhemiinattentionor
extinctiontomorethanonemodality
doesnotrecognizeownhandororients
toonlyonesideofspace.

_____

takenasevidenceofabnormality.Since
theabnormalityisscoredonlyifpresent,
theitemisneveruntestable.

_____

Adaptedfrom:GoldsteinLB,SamsaGP,Stroke199728:307.
Graphic61698Version4.0

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Antithrombotictreatmentofacuteischemicstrokeandtransientischemicattack

Disclosures

Disclosures:Jam aryOliveiraFilho,MD,MS,PhDNothingtodisclose.WalterJKoroshetz,MDNothingtodisclose.ScottEKasner,MD
(Ticagrelor)].Consultant/AdvisoryBoards:Medtronic[Stroke,atrialfibrillation(CoreValve,REVEAL)]Merck[Stroke]Pfizer[Stroke]Novartis[Stroke]
disclose.
Contributordisclosuresarereview edforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedbyvettingthroughamultileve
contentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.
Conflictofinterestpolicy

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