1. Endovascular thrombectomy can significantly improve outcomes for acute ischemic stroke patients compared to standard treatment with intravenous thrombolysis alone. The MR CLEAN trial showed improved functional independence and reduced disability with the addition of thrombectomy. 2. The EXTEND-IA trial also found better reperfusion and early neurological improvement when using perfusion imaging to select patients for thrombectomy among those who failed intravenous thrombolysis. Revascularization rates were higher compared to MR CLEAN. 3. The ESCAPE trial similarly found improved functional independence and reduced disability when adding thrombectomy for eligible patients within 12 hours of onset, confirming results of earlier trials.

1. Stroke & thrombectomy
Jo Caekebeke
VNV febr 2015

2. Reperfusion therapy for acute ischemic stroke
• Timely restoration of blood flow:
• Most effective maneuver for salvaging the penumbra

3. Time is brain
• Golden hour:
• From “door to needle” time (DTN)
• To “onset to treatment” time (OTT)
• Transport to hospital takes 40 to 50 min
• Each 15 min reduction in OTT:
• 4% increase in odds of mRS 0-3
• 4% decrease of symptomatic hemorrhagic transformation
1. Lansberg M. et al. Stroke 2009;40:2079-2084

4. IV thrombolysis
• NINDS tPA stroke trial
• MCA stroke within 3 h OTT
• IV tPA proved efficacy
• Higher rates of ICH: IV tPA vs controls: 6.4% vs 0.6%
• Meta-analysis of data from 6756 patients showed:
• Efficacy of IV tPA within 4.5 h of stroke onset
1. NINDS study group N Engl J Med 1995;333:1581-1587
2. Emberson J. et al. Lancet 2014;384:1929-1935
3. Lansberg M. et al. Stroke 2009;40:2438-2441

5. Recanalization
• Recanalization is associated with good outcome and reduced mortality
• IV tPA thrombolysis less effective in:
• More proximal occlusions
• In > ⅓ of acute anterior-circulation strokes
• Larger and older thromboemboli
• In situ thrombosis versus cardioembolic occlusion
• Recanalization rates:
• Spontaneous: 14% to 28 %
• Intravenous thrombolysis: 46.2 %
• Intra-arterial thrombolysis: 63.2 %
• Combined IV and IA thrombolysis: 67.5 %
• Mechanical thrombectomy: 83.6 %
1. Lima F. et al. JAMA 2014;71:151-157
2. Wolpert S. et al. AJNR 1993;14:3-13
3. Beumer D. et al. Cerebrovasc Dis 2013;35:Suppl:66
4. Heldner M. et al. Stroke 2013;44:1153-1157
5. Kassem-Moussa H. et al. Arch Neurol 2002;59(12):1870–1873

6. Reocclusion after IV tPA
• NINDS: 13% deteriorated clinically after initial improvement
• Reocclusion (by TCD) in 34%
• Case series (n=142): MCA occlusion (by TCD) and IV tPA
• MCA (partial) recanalization in 61%
• Clinical deterioration after initial improvement in 25%
• Early Reocclusion in 71% vs 12% of the series
• Predictors: NIHSS > 16, ipsilateral carotid stenosis or occlusion

7. Recanalization / reperfusion: TICI scale
• TICI: thrombolysis in cerebral infarction scale
• Grade 0: no perfusion
• Grade 1: perfusion past the initial obstruction but limited distal
branch filling with little or slow distal perfusion
• Grade 2a: perfusion of < 50% of the vascular distribution of the
occluded artery
• Grade 2b: perfusion of > 50% of the vascular distribution of the
occluded artery
• Grade 3: full perfusion with filling of all distal branches

8. TICI: varying definitions in the literature

9. ASPECTS: early ischemic changes: 10 → 0 points
• C- Caudate
• I- Insular ribbon
• IC- Internal Capsule
• L- Lentiform nucleus
• M1- Anterior MCA cortex
• M2- MCA cortex lateral to the
insular ribbon
• M3- Posterior MCA cortex
• M4, M5, M6 are the anterior,
lateral and posterior MCA
territories immediately superior
to M1, M2 and M3, rostral to
basal ganglia.
• Subcortical structures are
allotted 3 points (C, L, and IC).
• MCA cortex is allotted 7 points
(insular cortex, M1, M2, M3,
M4, M5, M6)

10. Ultrasound (TCD) enhanced IV thrombolysis
• Meta-analysis: 6 RCT’s, n = 224 and 3 nRCT’s, n = 192
• High-frequency ultrasound enhanced thrombolysis versus tPA alone
• Recanalization: 37% versus 17%
• mRS: significantly better
• Meta-analysis: 5 RCT’s, n = 233
• Recanalization: significantly more likely
• mRS: no significant difference
• CLOTBUST trial, n = 126, part of both meta-analyses
• MCA occlusion
• Recanalization: 38% versus 13%
• mRS: non-significant positive trend

11. IA thrombolysis
• PROACT II trial, n = 180
• MCA stroke, OTT < 6h
• No major infarct on CT
• Occlusion M1 or M2
• IA r-proUK plus heparine versus heparin alone
• No mechanical clot disruption allowed
• No IV tPA control group
• Recanalization: 66% versus 18%
• mRS 0-2: 40% versus 25%
• (mRS 0-2: 31% with IV tPA in NINDS trial)
• Confirmed by a meta-analysis of 5 RCT’s, n = 395
• PROACT II included
1. Furlan A. et al. JAMA 1999;282:2003-2011

12. Combined IV & IA thrombolysis: negative trials
• IMS II trial (interventional management of stroke)
• OTT < 3h
• First ⅔ IV tPA dosis
• 15% as bolus, remaining in 30 min
• After bolus: angiography
• If clot identified: remaining ⅓ dose IA in the clot
• If no clot: remaining ⅓ dose IV
• Benefit not statistically significant
• Compared with historical NINDS tPA trial
• RECANALISE prospective registry
• Combined IV/IA tPA versus IV tPA (≈ IMS II protocol)
• Recanalization: 87% vs 52%
• Early recovery (NIHSS 0/1 or 4 pt improvement): 60% vs 39%
• mRS 0-2: 57% vs 44%
1. IMS II investigators Stroke 2007;38:2127-2135
2. Mazighi M. et al. Lancet Neurol 2009;8:802-809

13. IV & IA thrombolysis & thrombectomy: negative trials
• IMS III trial(interventional management of stroke)
• IV tPA (n = 222) versus
• IV & IA tPA or mechanical thrombectomy (n = 434)
• SYNTHESIS Expansion trial, n = 362
• IV tPA < 4.5h versus
• IA tPA and/or thrombectomy < 6h
• MR-RESCUE (mechanical retrieval and recanalization of stroke clots using
embolectomy)
• Based on penumbra imaging
• Thrombectomy with Merci or Penumbra devices < 8h
• Long OTT: delay in time to reperfusion ≈ worse outcome
• No pretreatment confirmation of proximal intracranial occlusion
• Limited use of third-generation devices, lower rate of recanalization
• Subgroup with TICI 2b/3 ≈ better outcome
1. Broderick J. et al. N Engl J Med 2013;368:893-903
2. Davis S. et al. Curr Opin Neurol 2005;18:47-52
3. Kidwell C. et al. N Engl J Med 2013;368:914-923

14. From 2013 bear to 2014 bull stroke market

15. Cerebral PTA with stent placement
• SARIS trial, preliminary data of first n = 20
• Balloon angioplasty (PTA) and stent placement
• Recanalization in 100%
• 5% symptomatic and 10% asymptomatic hemorrhage
• Trial, n = 105
• Stroke with MCA occlusion:
• After IV tPA failure (TCD at 60 min) or IV tPA contraindication
• PTA + stent < 8h or no further therapy:
• Recanalization: 92.6% (TICI 2a - 3)
• 4% risk of symptomatic intracerebral hemorrhage.
• Concerns about:
• Need for dual anti-platelet therapy
• Increased risk of hemorrhage
• Possible in-stent stenosis
1. Roubec M. et al. Radiology 2013;266:871-878

16. Cerebral PTA with stent placement
1. Roubec M. et al. Radiology 2013;266:871-878
IVtPAsuccessful
(n=26)
IVtPAfailure
PTA+stent(n=23)
IVtPAfailure
noPTA(n=26)
IVtPA
contraindication
PTA+stent(n=31)
IVtPA
contraindicationno
PTA(n=25)

17. Mechanical endovascular intervention: MR CLEAN
• Usual care alone (IV tPA) versus usual care + IA treatment
• n = 500: control group n = 267, IA group n = 233
• IV tPA in 90% in each group
• < 6h (360 min) OTT
• IA treatment: thrombolysis, thrombectomy or both
• IA thrombolysis
• IA tPA: max 90 mg or only 30 mg if IV tPA
• Urokinase: 1.2*106 IU or 0.4*106 IU if IV tPA
• Mechanical thrombectomy
• Thrombus retraction, aspiration, wire disruption, retrievable
stent
1. Berkhemer O. et al. N Engl J Med 2014 DOI:1056/NEJMoa1411587

18. MR CLEAN
• Confirmed proximal occlusion in anterior cerebral circulation
• Distal ICA, M1, M2, A1, A2 on CTA, MRA, DSA
• Additional extracranial ICA occlusion or dissection allowed
• CT perfusion was not required but performed in 65%
• Occlusion site
• Intracranial ICA: 0.4% 1.1%
• ICA and M1 25.3% 28.2%
• M1 66.1% 62%
• M2 7.7% 7.9%
• A1 or A2 0.4% 0.8%
• Extracranial ICA 32.2% 26.3%
1. Berkhemer O. et al. N Engl J Med 2014 DOI:1056/NEJMoa1411587

19. MR CLEAN
• Intra-arterial therapy in 84.1% (in 196 of 233 pt)
• Mechanical thrombectomy in 83.7%
• Retrievable stents in 81.5% and other devices in 2.1%
• Additional IA thrombolysis in 10.3% and as monotherapy in 0.4%
• Also carotid stenting in 12.9%
• General anesthesia in 37.8%
• Times: IV/IA ϴ versus IV ϴ:
• Onset to IV tPA treatment time (OTT):
• 85 min vs 87 min
• IA therapy: onset to groin puncture time:
• 260 min (4h 20min)
1. Berkhemer O. et al. N Engl J Med 2014 DOI:1056/NEJMoa1411587

20. MR CLEAN results
• mRS: better after IA ϴ: Δ 13.5% mRS 0-2
• NIHSS: better after IA ϴ: Δ 2.9 points (1.5-4.3)
• Barthel index: better after IA ϴ
• Recanalization on follow-up CTA: 75.4% vs 32.9%
• TICI 2b/3 on DSA: 58.7%
• Infarct volume (ml) less after IA ϴ: Δ 19 ml (3-34)
• No significant difference in symptomatic intracranial hemorrhage, death
• More new ischemic strokes in different territory 5.6% vs 0.4%
1. Berkhemer O. et al. N Engl J Med 2014 DOI:1056/NEJMoa1411587

21. MR CLEAN results
1. Berkhemer O. et al. N Engl J Med 2014 DOI:1056/NEJMoa1411587

22. Endovascular therapy with perfusion-imaging selection
• EXTEND-IA trial, n = 70: stopped early because of proven efficacy
• IV tPA alone (n = 35) versus IV tPA + thrombectomy (n = 35)
• Selection: ICA, M1, M2 occlusion and evidence of salvageable tissue
• CTA < 4.5h
• CT perfusion imaging (RAPID software)
• Irreversibly injured ischemic core: relative CBF < 30%
• Hypoperfused (salvageable) ischemic penumbra: Tmax > 6s
• Occlusion confirmed with DSA
• Solitaire FR stent retriever
• Outcomes
• Reperfusion: reduction in perfusion-lesion volume
• Early neurologic improvement: NIHSS reduction
• mRS at 90 days
• Symptomatic intracranial hemorrhage
1. Campbell B. et al. NEJM 2015; Feb 23: 1-10 DOI: 10.1056/NEJMoa1414792

23. EXTEND-IA
1. Campbell B. et al. NEJM 2015; Feb 23: 1-10 DOI: 10.1056/NEJMoa1414792

24. EXTEND-IA
1. Campbell B. et al. NEJM 2015; Feb 23: 1-10 DOI: 10.1056/NEJMoa1414792
Onset tot puncture: 3h30min

25. EXTEND-IA
• mRS 0-2 at 90 days: NNT 3
1. Campbell B. et al. NEJM 2015; Feb 23: 1-10 DOI: 10.1056/NEJMoa1414792

26. EXTEND-IA
• 25% were excluded on the basis of large ischemic cores without significant
salvageable ischemic brain
• < 4.5h: in unselected population 10 to 15% have large ischemic cores
• Volume-based criteria do not account for the location of the core
• Although relevant to the clinical outcome
• Excluded patients might have benefited from thrombectomy
• Shorter time to onset of treatment
• Not waiting for clinical response to tPA
• From onset to groin puncture: 50 min shorter than MR CLEAN
• Improved rates of recanalization
• In 86% recanalization of > 50% versus 58% in MR CLEAN
• Reocclusion after 24h was uncommon
• 11% had no retrievable thrombus on angiography
1. Campbell B. et al. NEJM 2015; Feb 23: 1-10 DOI: 10.1056/NEJMoa1414792

27. ESCAPE
• N = 316, prematurely stopped after positive interim analysis
• Inclusion < 12h after onset
• N = 150: standard care (IV tPA if eligible, < 4.5h, n = 118) versus
• N = 165: standard care (IV tPA if eligible, < 4.5h, n = 120) + thrombectomy
• CT/CTA: occlusion ICA or M1 or M2
• ASPECTS > 5 and good collaterals
• Thrombectomy < 6h, Solitaire FR stent retriever
• Recanalization: 72.4%
• mRS 0-2: 53% vs 29.3%
• Symptomatic intracranial hemorrhage: 3.6% vs 2.7%
1. Goyal M. et al. NEJM 2015; Feb 11, DOI: 10.1056/NEJMoa1414905

28. ESCAPE
• Occlusion location
• ICA + M1: 27.6% 26.5%
• M1 or all M2 segments: 68.1% 71.4%
• Single M2 segment: 3.7% 2%
• Ipsilateral cervical ICA: 12.7% 12.7%
• Times:
• Onset to IV tPA: 110 min 125 min
• CT to groin puncture (PTP): 51 min
• CT to first reperfusion: 84 min
• Onset to first reperfusion: 241 min (4h)
1. Goyal M. et al. NEJM 2015; Feb 11, DOI: 10.1056/NEJMoa1414905

29. ESCAPE
1. Goyal M. et al. NEJM 2015; Feb 11, DOI: 10.1056/NEJMoa1414905

30. ESCAPE
1. Goyal M. et al. NEJM 2015; Feb 11, DOI: 10.1056/NEJMoa1414905

31. SWIFT PRIME
• N = 196, prematurely stopped after positive interim analysis
• IV tPA alone (< 4.5h) (n = 93) versus IV tPA + thrombectomy (n = 98)
• CTA or MRA: occlusion ICA or M1
• Without extracranial carotid occlusion
• ASPECTS > 6
• CT hypodensity (or MRI hyper) < 1/3 MCA territory
• Thrombectomy < 6h, Solitaire FR stent retriever
• Recanalization: 88%
• mRS 0-2: 60.2% vs 35.5%
• Symptomatic intracranial hemorrhage: 1% in IA group
• Times:
• CTA to groin puncture (picture to puncture PTP): 58 min
• Onset to device deployment: 252 min (4h 12min)
1. Saver J. Oral Presentation, Int Stroke Conference 2015

32. Neurothrombectomy devices
• Distally deployed devices
• Passed beyond occlusion prior to device deployment
• Merci Retriever: corkscrew retrieval device (with web of arcading
filaments)
• Proximally deployed devices
• Clot grasped or aspirated from proximal vasculature
• Penumbra Thromboaspiration System

33. Neurothrombectomy devices: stent retrievers
• Intra-clot deployed devices
• Solitaire Flow Restoration Device
• Trevo Retriever
• Hybrid between a self-expanding stent and a soft “spider-web-like”
basket for clot removal = angioplasty + stenting + clot extraction
• SWIFT trial testing the solitaire stent retriever vs Merci device
• TREVO-2 trial testing trevo stent retriever vs Merci device
1. T

34. To tube or not to tube ?
• Choice of anesthesia depends on the individual situation
• Severe agitation
• Low level of consciousness (GCS < 8)
• Loss of airway protective reflexes
• Respiratory compromise
• Retrospective analysis (n = 507) supports conscious sedation
• General anesthesia versus conscious sedation
• Hospital mortality: 25% vs 12%
• Pneumonia: 17% vs 9.3%
1. Herrmann O. et al. Neurocrit Care 2012;17:354-360
2. McDonald J. et al. J Neurointerv Surg 2014

35. To tube or not to tube ?
• Poorer outcome with general anesthesia due to:
1. Herrmann O. et al. Neurocrit Care 2012;17:354-360

36. Beyond the anterior circulation ?
• Limited data regarding acute basilar artery occlusion
• No reason to treat BA occlusion differently from AC ischemic stroke
• IV tPA may be effective at OTT > 6 h in BA occlusion without
extensive ischemia on baseline CT/MRI
• IV tPA + thrombectomy vs IV tPA alone trial
• BASICS trial is actually running
• Cerebral venous sinus thrombosis: case reports
• Thrombectomy with solitaire FR device
• Stepwise complete recanalization
• Indication: deterioration despite anticoagulation
1. Froehler M. J NeuroInterv Surg 2013 doi: 10.1136/neurintsurg-2012-010517

37. Tandem occlusions
• Tandem extracranial carotid artery and intracranial large vessel occlusions
• Carotid stenting and intracranial thrombectomy
• Carotid stenting successful in all cases
• TICI 2a, 2b, 3 in 91%
• mRS 0-2 in 52%
• Review of 32 studies (n = 1107)
• Stenting + thrombectomy versus IA thrombolysis
• Recanalization: 87% vs 48%
• mRS 0-2: 68% vs 15%
1. Heck D. et al. J Neurointerv Surg 2014; doi: 10.1136/neurintsurg-2014-011224
2. Cohen J. et al. J Neurointerv Surg 2014
3. Kappelhof M. et al. J Neurointerv Surg 2015;7:8-15

38. First we take STEMI than we take STROKE
• 2008: Stent for Life (SFL) Initiative is a highly successful model for STEMI
• Reperfusion within 20 to 25 min after arrival at the cathlab
• But in stroke there is the need for neurological and CT evaluation
• Two small single-centre thrombectomy studies without control group
• Recanalization in 83% and 89% and favorable outcome (mRS < 2) in
48% and 58%
1. Kala P. . EuroIntervention 2014;10:778-780
2. Widimsky P. et al. EuroIntervention 2014;10:869-875
3. Higashida R. et al. Stroke 2003;34:109-137

39. First we take STEMI then we take STROKE
• What can interventional cardiologists offer to stroke patients ?
• A STEMI network with 4/7 cathlabs
• Highly experienced interventional teams
• Fully equipped cathlabs
• High-quality X-ray equipment
• Excellent collaboration with EMS and use of telemedicine
• What do interventional cardiologists have to learn ?
• Flow grading systems: TICI3 and Mori classification
• NIHSS score
• Cerebral anatomy/function by CT/MRI
• Dedicated diagnostic and therapeutic invasive techniques and tools
• mRS score
1. Kala P. . EuroIntervention 2014;10:778-780
2. Widimsky P. et al. EuroIntervention 2014;10:869-875
3. Higashida R. et al. Stroke 2003;34:109-137

40. Recommendations: ESO, ESMINT, ESNR, 20/02/2015
• Mechanical thrombectomy, after IV tPA within 4.5h when eligible, for strokes
with large artery occlusions in anterior circulation up to 6h after onset
• Thrombectomy should not prevent early IV tPA
• IV tPA should not delay thrombectomy
• Thrombectomy should be performed ASAP with stent retrievers
• Other devices may be used if rapid, complete, safe reperfusion can be achieved
• If IV tPA is contraindicated: thrombectomy is first-line treatment in large vessel
occlusions
• Acute basilar artery occlusion: thrombectomy after IV tPA when indicated
• Multidisciplinary team, experienced centers an neuro-interventionalist
• Choice of anesthesia depends on the individual situations, avoiding
thrombectomy delays
• Intracranial vessel occlusion diagnosed with non-invasive imaging
• If vessel imaging not available:
• NIHSS > 9 within 3h or > 7 within 6h may indicate large vessel occlusion
• Signs of large infarction (ASPECTS) may be unsuitable for thrombectomy
• Penumbra imaging can be used and correlate with functional outcome
• High age alone is no contraindication for thrombectomy
• ESO Karolinska Stroke Update

41. Forget it, it’ all about FAST action