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Thrombectomy for ischemic stroke Prof Bruce Campbell Consultant Neurologist and Head of Stroke Royal Melbourne Hospital Professorial Fellow, University of Melbourne [email protected]
Thrombectomyforischemicstroke
ProfBruceCampbell
ConsultantNeurologistandHeadofStrokeRoyalMelbourneHospital
ProfessorialFellow,[email protected]
Disclosures Financialdisclosures–none
Off-labeluseoftenecteplaseforischaemicstroke
Learningobjectives Understandtheevidencebehindthrombectomyeligibility– siteofvesselocclusion– age– severity– time
Understandimagingstrategiesandtheprognosticsignificanceofischemiccorevolume
UnderstandtheroleofIVthrombolysisbeforethrombectomy– 0-4.5hrversus>4.5h
UnderstandthecriticalimportanceofSystemsofcareinmaximisingpatientoutcomes
Keymessages Endovascularthrombectomy(EVT)profoundlyreducesdisabilityin
abroadrangeofischemicstrokepatientswithlargevesselocclusion0-6hafterstrokeonset
EVTalsobenefitsselectedpatientswithfavorableperfusionimagingupto24hafterstrokeonset
CurrentlyEVTiscombinedwithIVthrombolysisineligiblepatients(withongoingtrialstestingEVTaloneinpatientspresentingdirectlytoEVTcenters)
Fastertreatmentisthemosteffectivewaytoimprovepatientoutcomes–streamlinetransfersandminimizere-imaging
Largevesselocclusion-thrombolysisvsthrombectomy
Thrombolysisonly
Thrombectomyonly
Thrombolysis&Thrombectomy
*“LVO”definitionmaychangewithdeviceimprovements
**plannedtrialstoaddIVlysistothrombectomy>4.5hr
>70%-noreperfusiontherapysuper-mild,established,verylate
largevesselocclusion(LVO) 15%ofallstrokebut 39%ofacutelypresentingstroke responsiblefor62%ofdependencyand
96%ofmortality(MalhotraFrontNeurol2017)
IVthrombolysishaslimitedefficacy
NewEngJMed2015: 5Positiverandomizedtrials 2Editorials Faster,betterreperfusion MoreImaging
Whichsitesofvesselocclusion?
ICAandM1–benefit tandemdisease(cervical+intracranial)–benefit ?M2 lesscommon,highlyvariableanatomy
smaller,moretortuous,lessaccessible
lessterritoryatrisk
greaterresponsetoIVthrombolysis
HERMESmeta-analysis=larger/dominant/moreproximalM2withhigherNIHSSbenefit–needtoindividualizedecision
M3/4,ACA,PCA-?? Basilar–excludedfrommosttrials,BEST20%benefit“astreated”,
BASICSRCTongoing.timewindow:?24hrfromlastknownwellvs~8hrfromonsetofcoma
ICA M1
?M2
not M3/4?
GoyaletalLancet2016
Agelimits?
AgeisprognosticAgedoesnotmodifytreatmenteffect
Severitylimits?
GoyaletalLancet2016
NIHSSisprognosticNIHSSdoesnotmodifytreatmenteffectUncertaintyinverymild(NIHSS0-5)àENDOLOWtrial
Thrombectomy– stilltimecritical
FransenJAMANeurology2016
MRCLEANselection(CTAocclusion)withsuccessfulreperfusion
Thrombectomy– stilltimecritical
7.3hrs
2.3 2.5 2.9
3.4 4.2
5.5 8.6
NNTs
SaverJAMA2016
Forevery4mindelayafterreachingemergency1in100patientswillhaveincreaseddisability
IschemicPenumbra–thereasonwecanimproveoutcomeafterischaemicstroke
Astrup,Symon1977
CTperfusion–diagnosisandprognosis
DelayedTTP/Tmax=collateralterritory
timeAreaundercurve≈0
conc
entr
atio
n
timeArea=CBV
TTP
conc
entr
atio
n
CBVLowCBV
=likelyirreversiblydamaged
CBF TTP
DiffusionMRI
AutomatedCTperfusionprocessing
“Howmuchbloodsupply”(severelyreduced≈dead)
relCBF<30%ofnormalbrainCampbelletalStroke2011
*timetoreperf&greyvswhitematter
“Howdelayedisthebloodsupply”(severelydelayed≈atrisk)
iSchemaViewRAPIDversion4.7
NogueiraNEJM2017
ordinalNNT2.0mRS0-2:49%vs13%,p<0.000184%mTICI2b/3SICH5.6%vs3.0%,p=0.50
ordinalNNT2.1
mRS0-245%vs17%,p<0.000176%mTICI2b/3SICH6.5%vs4.4%,p=0.75
AlbersNEJM2018
DAWNeligibilityeffectinDEFUSE3
AlbersetalNEJM2018
DEFUSE3criteria simpler ~60%morepatientseligible
Noreductionintreatmenteffectwithinage,NIHSSorcorevolumesincluded
i.e.6-24hrwithICA/M1and<70mLcoreàthrombectomy
DAW
Ne
ligib
le
no
tDAW
Ne
ligib
le
Istimestillbrain?
Overallstrokepopulationareverytimesensitive–stillneedtogoasfastaspossible
Theproportionofpatientswhoremaineligiblebyimagingcriteriadecreasesovertime(~50%ofLVOinthe6-24hrtimewindowbasedonDEFUSE3screening)
However,ifanindividualpatientisunavoidablydelayedinpresentationANDimagingisstillfavorablethentheyarelikelytobenefitfromreperfusion
Yes!
advancedimagingisnotjustabout“excluding”patients includingmorepatients
– mildNIHSSbutsignificantperfusionabnormality– late/unknowntime– “lowASPECTS”butonlymoderatevolumeNCCTchanges– clinically“marginal”butgoodimaging
AND diagnosticbenefits
– whenpatientspresentthefirstquestionis“isitstroke”– variablelevelsofexperienceonground,in-hours,after-hours,telemedicine– improvedNCCTinterpretationwhenyouknowwheretoscrutinize– LVOmaybechronic,partial,asymptomatic–perfusioncanhelp
AND Maybeinfuturewewillhavenon-reperfusion-basedtherapies…
– glyburide,NA1etcmightbenefitfromimagingtotargetthosenotlikelytodowelljustwithreperfusion
ImpactofCorevolume,AgeandTime(imagingtoreperfusion)onfunctionaloutcomeinpatientssuccessfullyreperfused
0 20 40 60 80 100
Age (years)
40
50
60
70
80
90 Imag
ing to
repe
rfusio
n (min)
50
100
150
200
250
% m
RS 0-2
0
20
40
60
80
100
Age (years)
40
50
60
70
80
90 Imag
ing to
repe
rfusio
n (min)
50
100
150
200
250
% m
RS 0-2
0
20
40
60
80
100
10mlcoremRS0-2 100mLcoremRS0-2
Age (years)
40
50
60
70
80
90 Imag
ing to
repe
rfusio
n (min)
50
100
150
200
250
% m
RS 0-30
20
40
60
80
100
100mLcoremRS0-3
For0-6hourpatientsdon’texcludepurelyonbasisofcorevolume:Balancecorevolumeandlocation,expectedtimetoreperfusion,pre-morbidstatus&toleranceofdisabilityifknown CampbelletalLancetNeurology2019
AllthepositiveRCTsadministeredalteplasetoalleligiblepatients…anditdoeshaveaneffect:
Ifeligibleforbothtreatmentsshouldwestillgivethrombolysisbeforethrombectomy?
IV-IAbridging DirectIA
potentialbenefitiffailure/delayinendovascularprocedure
potentialreductioninsymptomaticintracerebral(andsystemic)hemorrhage
potentialbenefitindissolvingdistalembolicfragmentsofthrombus/multi-territoryemboli
potentialreductionindistalmigration/fragmentationofthrombus“outofreach”priortoendovascularprocedure
potentialforpre-endovascularreperfusion savecostofalteplase/tenecteplase
Intervention Alteplase Standardcare
FinalReperfusionTICI2b/3[AngioCorelabdetermined]
77% --- ---
mAOL2-3(at2-8hCTA)[CTCorelabdetermined]
--- 37% 7%
GoyaletalESCAPE,NEJM2015
Meta-analysisofobservationaldata
MistryStroke2017
NBmostly“direct”patientswerelysis-ineligiblepatientsintendedforthrombectomywhorecanalizepriorwerenotincluded…
mRS0-2
DEATH
Recanwith≤2devicepasses
Recanalization
?thrombolysisfacilitatesthrombectomyevenifreperfusionnotachievedpriortoprocedure
SystemsofCare–TimeisBrain!
ConclusionsRapidreperfusionremainstheproventreatmentparadigminstroke Currentlythrombolysis+thrombectomyifeligibleforboth(DIRECTtrialsongoing)
ThrombectomyforICA,M1,tandem,basilar,selectedM2occlusions “Good”premorbidfunction Noageorclinicalseveritylimits 0-6h:broadimagingcriteria6-24h:DEFUSE3imagingselection<70mLcore CTperfusionisdiagnosticandcharacterizesirreversiblyinjuredcore/collaterals
-veryhelpfulforprognosisinanytimewindow Simplydeliveringthrombolysis&thrombectomyfasterandincreasingaccessto
appropriatepatientsisessentialtomaximizeeffectiveness–focusonsystemsofcare
~
