update phase aguë de l'avc€¦ · interact-2 trial: anderson c, lancet neurol 2008 atach-2...

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Centre Hospitalier Universitarie Vaudois Centre cerebrovasculaire Update phase aguë de l'AVC Chef de Clinique, Centre Cérébrovasculaire Service de Neurologie, Départment des Neurosciences Cliniques Dr. Davide Strambo 26 Septembre 2019

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Page 1: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

Centre Hospitalier Universitarie Vaudois Centre cerebrovasculaire

Updatephaseaguëdel'AVC

Chef de Clinique, Centre Cérébrovasculaire Service de Neurologie,

Départment des Neurosciences Cliniques

Dr. Davide Strambo

26Septembre2019

Page 2: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

Outline•  AVCischémique

–  Nouveautés•  Thrombolysepourdébutinconnu/auréveil•  Thrombectomietardive•  Thrombolysetardive

–  Perspectives•  Thrombectomiedirectevs.Bridging•  Tenecteplase

•  Hemorragiecérébrale•  Tensionarterielle•  Reversiondelacrase•  Transfusiondeplaquettes

Page 3: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

REVASCULARISATIONAIGUE

Page 4: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

REVASCULARISATIONAIGUE

Oùonétait…..

NINDS ECASS I

‘95

FDA �96

ECASS II ‘98

ATLANTIS �99

EMEA ‘02

ECASS III ‘08

IST-III ‘12

�14 MR-

CLEAN

‘13 SYNTHESIS MR-RESCUE

IMS-III

‘15 EXTEND-IA

ESCAPE SWIFT

REVASCAT

ENCHANTED ‘16

�17-’18 DAWN

DEFUSE

WAKE-UP ‘18

EXTEND-IV ‘19

Page 5: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

Trial

Fenêtrethérapeutique

NINDS

ECASSI

ECASSII

ATLANTIS

ECASSIII

IST-3

Guidelines

ThrombolyseIV-rtPAOùonétait…

4.5h3h 6h

EmbersonJ,Lancet2014;ESOguidelines,CerebrovascDis2008;PowersW,Stroke2018

5h

Page 6: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

ThrombectomieOùonétait…

Trial Fenêtrethérapeutique

MR-CLEAN

ESCAPE

EXTEND-IA

SWIFT-PRIME

REVASCAT

THRACE

Guidelines

6h 8h5h 12h

SaverJ,JAMA2016;TurcG,ESJ2018;PowersJ,Stroke2018

Page 7: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

Enresumé

IV Thrombolysis rtPA

4.5 - 8 hours

Endovascular if access. proximal occlusion

0 - 4.5 hours 8 – 24 hours

Oùonétait…

Strokeonsetorlastseenwell

CourtesyofProf.PatrikMichel

Page 8: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

Lesbarrieresàsurmonter

•  Debutinconnuouaureveil

•  ThrombolyseIV<4.5h

•  Thrombectomie<6-8h

Page 9: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

REVASCULARISATIONAIGUE

Lesnouveautés…

NINDS ECASS I

‘95

FDA �96

ECASS II ‘98

ATLANTIS �99

EMEA ‘02

ECASS III ‘08

IST-III ‘12

�14 MR-

CLEAN

‘13 SYNTHESIS MR-RESCUE

IMS-III

‘15 EXTEND-IA

ESCAPE SWIFT

REVASCAT

ENCHANTED ‘16

�17-’18 DAWN

DEFUSE

WAKE-UP ‘18

EXTEND-IV ‘19

Page 10: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

Lesbarrieresàsurmonter

•  Debutinconnuouaureveil

•  ThrombolyseIV<4.5h

•  Thrombectomie<6-8h

Page 11: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

Debutinconnu/aureveil

ThomallaG,LancetNeurol2011

Page 12: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

Debutinconnu/aureveil

ThomallaG,LancetNeurol2011

Page 13: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

Debutinconnu/aureveil

OR1.61(1.09to2.36)2

1FromEmbersonJ,Lancet20142ThomallaG.NEJM2018

Favorableclinicalresponse(OR)

Harm0.5 0.6 1.0 1.5 2

<3h

3–4.5h

WAKE-UPtrial

BenefitNoeffect

OR1.26(1.05to1.51)1

OR1.75(1.35to2.27)1

ThrombolyseIV

Page 14: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

Debutinconnu/aureveil

IV Thrombolysis rtPA

4.5 - 8 hours

Endovascular if access. proximal occlusion

0 - 4.5 hours 8 – 24 hours

Strokeonsetorlastseenwell

Ifonsetunknownoratwake-upàIVTrtPAifDWI+/FLAIR-

Page 15: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

Lesbarrieresàsuperer

•  Debutinconnuouaureveil

•  ThrombolyseIV<4.5h

•  Thrombectomie<6-8h

Page 16: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

Leconceptdumismatchcore/penombre•  Ischemieirreversibile

(core)–  MRI-DWI–  CTnatif–  CTdeperfusion

•  Ischemiereversible(penombre)–  MRIdeperfusion–  CTdeperfusion–  Deficitclinique

Page 17: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

Leconceptdumismatchcore/penombre•  Ischemieirreversibile

(core)–  MRI-DWI–  CTnatif–  CTdeperfusion

•  Ischemiereversible(penombre)–  MRIdeperfusion–  CTdeperfusion–  Deficitclinique

Page 18: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

L’applicationduconceptdumismatch

OR1.86(1.15to2.99)

MaH,NEJM2019;CampbellB,Lancet2019;

NogueiraR,NEJM2017;AlbersG,NEJM2018;SnellingB,JNeurosciRuralPract2019

Favorableclinicalresponse(OR)

Harm0.3 1.0 3

<3h

4.5-9hMissmatch+

BenefitNoeffect

OR1.75(1.35to2.27)ThrombolyseIV

0.5 2 50.2

Page 19: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

L’applicationduconceptdumismatch

OR1.86(1.15to2.99)

MaH,NEJM2019;CampbellB,Lancet2019;

NogueiraR,NEJM2017;AlbersG,NEJM2018;SnellingB,JNeurosciRuralPract2019

Favorableclinicalresponse(OR)

Harm0.3 1.0 3

<3h

4.5-9hMissmatch+

BenefitNoeffect

OR1.75(1.35to2.27)ThrombolyseIV

Thrombectomie<6-8h

6-24hMissmatch+

0.5 2 50.2

OR4.02(2.02to8.02)OR6.25(3.12to12.5)

OR2.49(1.76to3.53)

DAWN

DEFUSE-3

Page 20: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

Enresumé

IV Thrombolysis rtPA

4.5 - 8 hours

Endovascular if access. proximal occlusion

0 - 4.5 hours 8 – 24 hours

Lesnouveautées…

Strokeonsetorlastseenwell

Page 21: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

Enresumé

EmbersonJ,Lancet2014;SaverJ,JAMA2016;NogueiraR,NEJM2017;AlbersG,NEJM2018;MaH,NEJM2019;CampbellB,Lancet2019

IV Thrombolysis rtPA

4.5 - 8 hours

Endovascular if access. proximal occlusion

0 - 4.5 hours

Late IV thrombolysis rtPA if mismatch criteria met

EVT if LVO and mismatch criteria met

Lesnouveautées…

Strokeonsetorlastseenwell

Ifonsetunknown/wake-upIVTrtPAifDWI+/FLAIR-

8 - 9 - 24 hours

Page 22: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

Enresumé

EmbersonJ,Lancet2014;SaverJ,JAMA2016;NogueiraR,NEJM2017;AlbersG,NEJM2018;MaH,NEJM2019;CampbellB,Lancet2019

IV Thrombolysis rtPA

4.5 - 8 hours

Endovascular if access. proximal occlusion

0 - 4.5 hours

Late IV thrombolysis rtPA if mismatch criteria met

EVT if LVO and mismatch criteria met

Lesnouveautées…

Strokeonsetorlastseenwell

Ifonsetunknown/wake-upIVTrtPAifDWI+/FLAIR-

8 - 9 - 24 hours

Page 23: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

REVASCULARISATIONAIGUE

Perspectivespourl’avenir…

NINDS ECASS I

‘95

FDA �96

ECASS II ‘98

ATLANTIS �99

EMEA ‘02

ECASS III ‘08

IST-III ‘12

�14 MR-

CLEAN

‘13 SYNTHESIS MR-RESCUE

IMS-III

‘15 EXTEND-IA

ESCAPE SWIFT

REVASCAT

ENCHANTED ‘16

�17-’18 DAWN

DEFUSE

WAKE-UP ‘18

EXTEND-IV ‘19

Page 24: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

Bridging?

IV Thrombolysis rtPA

4.5 - 8 hours

Endovascular if access. proximal occlusion

0 - 4.5 hours 8 – 24 hours

Late IV thrombolysis rtPA if mismatch criteria met

EVT if LVO and mismatch criteria met

Perspectivespourl’avenir

Strokeonsetorlastseenwell

SWIFT-DIRECTMRCLEAN-NOIV

Ifonsetunknown/wake-upIVTrtPAifDWI+/FLAIR-

Page 25: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

IV Thrombolysis rtPA

Tenecteplase?

4.5 - 8 hours

Endovascular if access. proximal occlusion

0 - 4.5 hours 8 – 24 hours

EVT if LVO and mismatch criteria met

Perspectivespourl’avenir

Strokeonsetorlastseenwell

TNK?

CouttsS,IntJStroke2018BurgosA&SaverJ,Stroke2019;

Hill&Michel,Stroke2019

Late IV thrombolysis rtPA if mismatch criteria met

Ifonsetunknown/wake-upIVTrtPAifDWI+/FLAIR-

TNK?

TNK?

Page 26: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

TRAITEMENTAIGUDEL’HEMORRAGIECÉRÉBRALELesnouveautés…

Page 27: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

Traitementaigudel’hemorragiecérébrale

•  Traitementaggressifdelatensionarterielle

•  Reversiondela

crase•  Plaquettes

•  Traitementaggressifdelatensionarterielle

•  Reversiondela

crase•  Transfusionde

plaquettes

Page 28: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

Hemorragiecérébrale

•  Traitementaggressifdelatensionarterielle

•  Reversiondela

crase•  Plaquettes

•  Traitementaggressifdelatensionarterielle

•  Reversiondela

crase•  Transfusionde

plaquettes

OR1.11(1.05to1.17)

Favorableclinicalresponse(OR)

Harm0.5 0.6 1.0 1.5 2

10mmHgreductiondelaTA

systolique

BenefitNoeffect

INTERACT-2Trial:AndersonC,LancetNeurol2008ATACH-2Trial:QureshiA,NEJM2016

MoullaaliT,LancetNeurol2019HemphillJC,Stroke2015;SteinerT,IntJStroke2014

Dansles6heuresaprèsledebutdel’HICSilaTAsystoliqueest>150mmHgàTargetTAS<140mmHgdans1heure

Pasdeconcernesurlasecurité

Page 29: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

Hemorragiecérébrale(sousanticoagulants)

•  Traitementaggressifdelatensionarterielle

•  Reversiondela

crase•  Plaquettes

Dabigatranàidarucizumab(Praxbind®)•  DisponibleenSuissedepuis2016•  DisponibleauCHUV•  Cout~3’000.-Apixaban,rivaroxaban,edoxabanàandexanetalfa(Ondexxya®)•  AutoriséparEMA•  BientotdisponibleenSuisse•  $$$$$$$$$$$$$$$$$•  Indicationsàdéfinir

•  Traitementaggressifdelatensionarterielle

•  Reversiondela

crase•  Transfusionde

plaquettes

RE-VERSEAD:PollackC,NEJM2017ANNEXA-4:ConnollyS,NEJM2019

Page 30: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

Hemorragiecérébrale(sousantiplaquettaires)

•  Traitementaggressifdelatensionarterielle

•  Reversiondela

crase•  Transfusionde

plaquettes

PATCHtrial:BaharogluMI,Lancet2016

OR0.48(0.28to0.85)

Favorableclinicalresponse(OR)

Harm0.2 0.5 1.0 2 5

Transfusiondeplaquettes

BenefitNoeffect

Pasdebenefice,probablementplusd’effetssecondairesHemorragiesseveres(GCS<8)excluesdel’étude

Page 31: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

TakehomemessagesAVCischemique•  L’imagerieavancépermetdeselectionnerlespatientspour

revascularizationjusqu’à24heuresHemorragiecèrèbrale•  Baisserlatensionarteriellesystolique<140mmHg•  Reverserlacrase•  Pasdetransfusiondeplaquettespourhemorragieslegeres/moderéssous

antiplaquettaires

Page 32: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner
Page 33: Update phase aguë de l'AVC€¦ · INTERACT-2 Trial: Anderson C, Lancet Neurol 2008 ATACH-2 Trial: Qureshi A, NEJM 2016 Moullaali T, Lancet Neurol 2019 Hemphill JC, Stroke 2015;Steiner

Centre Hospitalier Universitarie Vaudois Centre cerebrovasculaire

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