acute management of stroke due to intracranial...

Acute Management of Stroke due to Intracranial Steno-occlusion

Joon-Tae Kim, MD, PhD

Department of Neurology

Chonnam National University Hospital

Disclosure

• None

Contents

• Current status of acute management in AIS with LVO

– Endovascular therapy

• AIS with ICAD

– Characteristics

– Acute management of ICAD



• AIS with ICAD

– Characteristics


• IMS-3

• MR-RESCUE

• SYNTHESIS

2013 NEJM

• MR-CLEAN

• EXTEND-IA

• ESCAPE

• SWIFT-PRIME

• REVASCAT

2015 NEJMMain reasons for the success of recent RCTs

1. strict selection of patients with favorable imaging profiles;

2. quality control to decrease intra-hospital time delay esp. onset-

to-groin puncture time;

3. development of modern up-to-date thrombectomy devices with

increase in successful reperfusion

The recent success of 5 RCTs of endovascular thrombectomy (EVT) for

treating acute ischemic stroke (AIS) had resulted in EVT being

considered as the standard care treatment in clinical practice.

Lancet. 2016

5 RCTs

Pooled data for 1287 patients; 634 EVT vs 653 standard therapy

Time from onset to random; 3h 16m

Of 570 patients assigned EVT, 71% had mTICI 2b-3

mRS 0-2 at 90d: adjusted OR 2.71 (2.07-3.55; p<0.0001); NNT 5.1

NNT to have reduced disability of at least 1 point on mRS: 2.6

26.5%

46.0%

✓ For the primary outcome, pooled data showed reduced chance of

disability at 90d in patients assigned to thrombectomy vs those

assigned to control (adjusted cOR 2.49, 95% CI 1.76–3.53).

✓ The number needed to treat for one patient to have reduced

disability of at least 1 point on mRS was 2.6.

✓ Endovascular thrombectomy is of benefit to most patients with acute

ischemic stroke with anterior large vessel occlusion, irrespective of

patient characteristics or geographical location.

✓ About 30% of patients treated with EVT do not achieve substantial

reperfusion …

▪ EVT failures of reperfusion may result from

1) anatomical problems (tortuosity)

2) large clot amounts

3) tandem occlusion

4) clot characteristics

5) different pathomechanisms (embolic vs athero)

✓ The lack of effectiveness of retrievable stents in patients with

atherothrombotic stroke compared with the other etiologies.

✓ Although retrievable stents were the first choice device, intrinsic

characteristics of atherothrombotic lesions usually determined the

need to use other devices.

Matias-Guiu JA, et al. JNIS 2012

From heart From carotid artery

or

MCA occlusion

In situ thrombosis

When we encounter AIS patients with dICA or MCA occlusion,

we can presume two possible mechanisms,

embolic from heart or proximal artery or

thrombotic occlusion in the parent artery



• AIS with ICAD

– Characteristics


Intracranial atherosclerotic diseases

• Common in Asians, Hispanics, and non-white people in the

USA.

• ICAS is estimated to account for 33-50% of stroke in Chinese

populations, 47% in Thailand, and 28-60% in Korea.

• In the USA, the relative rate of strokes associated with ICAS

is about 5.0 times higher for Hispanics and 5.85 times higher

for black people compared with white people.

Kim JS, Intracranial Atherosclerosis

Wong LKS, Int J Stroke 2006

Nam HS et al. Neurology 2006

Bang OY et al. Neurology 2005

Intracranial atherosclerotic diseases

• Common in Asians, Hispanics, and non-white people in the

USA.

• ICAS is estimated to account for 33-50% of stroke in Chinese

populations, 47% in Thailand, and 28-60% in Korea.

• In the USA, the relative rate of strokes associated with ICAS

is about 5.0 times higher for Hispanics and 5.85 times higher

for black people compared with white people.


Wong LKS, Int J Stroke 2006

Nam HS et al. Neurology 2006

Bang OY et al. Neurology 2005

Thus, acute occlusion due to ICAD should not be ignored

in non-white people, especially Asian patients.

• Characteristics of ICAS-related occlusion

– Clinical

– Imaging

• Mechanisms of ischemic stroke and TIA in patients with ICAS

Mechanism Frequency Patterns of infarcts Number of

infarcts

In situ thrombotic

occlusion

Uncommon Large subcortical

Sometimes with BZ

Rarely, whole territory

Single

Sometimes

enlarging

A-to-A embolism Common Small cortical and

subcortical

Multiple

Impaired clearance of

emboli

Common Small, scattered, alongside

the BZ region

Multiple

Branch occlusive

disease

Common Small subcortical, lacune-

like

Single

Hemodynamic Uncommon Borderzone Multiple


• Hwang et al.

– reported the baseline and follow-up characteristics of residual stenosis

after EVT in relation to stroke pathogenesis

– 40 of 163 patients (24.5%) were found to have in-situ thrombotic

occlusion (IST)

Hwang et al. Stroke 2016

Hwang et al. Stroke 2016

Baseline Characteristics, Imaging, and Clinical Outcomes Based on the Operationally

Defined Target Arterial Lesion Pathogeneses

ICAS-related occlusion

MH Perez, et al. Stroke. 2017.

– It is essential to determine whether a remnant focal stenosis is

significant following primary thrombectomy (underlying ICAS)

• Hwang YH et al. 21.6%

• Lee JS et al. 17%

• Yoon W et al. 23%

The arteries that reoccluded had such a severe stenosis that most

patients showed a residual stenosis of 50%.

The degree of stenosis was significantly higher for patients with

reocclusion than those without.

Heo JH et al. Neurology 2003

Acute management of stroke due to ICAD

• Irrespective of mechanism of large vessel occlusion,

– Early recanalization/reperfusion is strongly associated with improved

functional outcome and reduced mortality

Rha JH, Saver JL, Stroke 2007

• Therapeutic strategy for acute occlusion due to ICAD

– No RCTs

– Primary therapy could be mechanical thrombectomy (IVT+EVT, if

possible)

Lee JS et al. J Stroke 2017


– No RCTs


possible)

✓ Among 53 patients underwent EVT with the Solitaire FR device, ICAS-related LVO

was observed in 9 (17%)

✓ Immediate reperfusion (mTICI 2b-3); 7 (77.8%)

✓ Partical recanalization (AOL 2-3); 6 (66.7%)



– No RCTs


possible)

✓ In situ thrombi could be removed well by recent

thrombectomy devices, and partial revascularization was

achieved in most cases.

✓ Stent retrieval could work well as the primary EVT


Cao X et al. Stroke 2016


– No RCTs


possible)

– However, there are concerns regarding endothelial damage if an acute

LVO is due to ICAD.

– The intrinsic atherosclerotic pathology and the severity of target

artery lesion may be pivotal factors associated with re-occlusion after

EVT

in situ thrombosis in ICAS lesion

Stent retrieval for ICAS-O. Routine first-

line thrombectomy can effectively

eliminate the major portion of in situ

thrombi.

Endothelial cells are still inflamed and

may cause re-occlusion.


• Therapeutic strategy for acute occlusion due to ICAD (2)

– Anti-thrombotics such as GP IIb/IIIa inhibitor

• Abciximab

• Tirofiban

Heo JH et al. Neurology 2003


– Anti-thrombotics such as GP IIb/IIIa inhibitor

Prospective study from a single center

IA-thrombolysis

Recanalized arteries were re-examined 20 min later

29 (13 men, 64yr) were treated with IAT/IV+IAT.

Initial recanalization was achieved in 18 (62%),

but unsuccessful in 11 patients.

Re-occlusion occurred in 4 of 18 patients (22%).

Systematically administrated abciximab was

associated with dissolution of the thrombus in

all reocclusion patients with 30-40 min after

the bolus.

prospectively collected data of consecutive patients with AIS in whom mechanical thrombectomy was

perfomed in the years 2006 to 2011.

In endovascular stroke therapy, additional treatment with the GP-IIb/IIIa inhibitor tirofiban is associated

with increased risk of fatal ICH and poor outcome.

tirofiban was given within a standard operational

procedure stating, “if stenting is performed or relevant

endothelial damage is feared, eg, because of multiple

thrombectomy passages.”

- the bias resulting in increased ICH was introduced by

the interventionalist administering tirofiban in patients

felt to be at higher risk of unfavorable outcome during

the intervention.

A retrospective study from a single center

IAT; 30 patients

IA tirofiban (Aggrastat®); 16 patients

… infused IA tirofiban with mechanical

thrombolysis with microwire if there was no

response to IA thrombolysis or suspicion of

reocclusion of partially recanalized vessel.

-TICI 2b-3; 13 of 16 patients

-No procedure related complications

-mRS 0-2 at 3m; 8/16 (50%)

-Mortality; 3/16 (18.9%)

-SICH; 1/16 (6.2%)

IST; 30.3% (40/132)

Instant reoclcusion; 65% (26/40) in the IST cohort

vs 3.3% (3/92) in the non-IST cohort

For the 35 patients with re-occlusion,

- 85.7% (30/35) had TICI 2/3

- 74.3% (26/35) had mTICI 2b/3 recanalization

- Rescue stenting was inevitable for 5 (14.3%)

- No SICH

a) Cerebral angiography revealed an occlusion at the M1 of the RMCA

b) Suction thrombectomy with Penumbra reperfusion catheter was performed,

and the following angiography showed a successful recanalization with

focal significant residual stenosis at the occlusion site

– The use of glycoprotein IIb/IIIa inhibitors appears to be potential

treatment…

– Limitations

• Retrospective analysis; neither randomized, nor blinded outcome measure…

• Small sample

• No standard dose for IA/IV-antithrombotics; lower dose of IV-tirofiban (0.5-1mg)

• dICAS/MCA occlusion are occasionally refractory to GP IIb/IIIa inhibitors

• Concerns of bleeding still continue…

– Further studies on GP IIb/IIIa inhibitor should be performed…


– Angioplasty and stenting

• Historical development of Endovascular technologies for

acute recanalization

Technology First human studies

IA microcatheter lysis 1988 (1999)

IA angioplasty 1994

IA aspiration thrombectomy 2001 (2009)

IA ultrasound sonothrombolysis 2003

IA implanted stents 2003

IA laser clot destruction 2004

IA Archimedes screw 2004

IA coil retrievers 2004

IA basket/brush retrievers 2006

IA stent retrievers 2010 (2010)

Stroke. 2009

- prospective single-arm trial

- Recanalization: in all 20 patients

: 12 (60%) TIMI 3

: 8 (40%) TIMI 2

- Thirteen (65%) patients: improvement of ≥4 NIHSS

- No SICH but the 1-month mortality rate was 25%

(5 patients).

These data appear to support the relative safety and angiographic

efficacy of a primary stent-for-stroke treatment paradigm.

Stroke. 2016

Neurosurgery. 2015

Stroke. 2017

J Stroke. 2016

A, the right carotid angiography showed an occlusion (arrow)

in the proximal M1 segment of the right MCA.

B, angiography after 1 passage of the Solitaire stent revealed a

severe stenosis (arrow) in the mid-M1 segment of the right

MCA.

C, angiography after intracranial angioplasty and stenting

showed recanalization of the right MCA and complete

reperfusion in the right MCA territory. Arrows indicate the

proximal and distal end of the Wingspan stent.

D, Maximum-intensity projection image of the follow-up CTA 1

week after the procedure showed that the stented segment of

the right MCA appeared widely patent (arrows).

Yoon W, Neurosurgery. 2015

After EVT (multimodal) Hwang YH et al.

2016

Baek JH et al.

2016

Yoon W et al.

2015

Lee JS et al.

2016

Primary IAT failure 53/208 (25.5%) NA

Adjuvant therapy

GP IIb/IIIa inhibitor 15/20 (67%) 17/53 (32%) None 2/9 (22.2%)

Angioplasty/Stenting 4/20 (20%) 17/45 (38%) 38/40 (95%) 5/9 (56%)

mTICI 2b-3

GP IIb/IIIa inhibitor NA NA NA

Stenting NA 14/17 (83.3%) 36/38 (95%)

mRS 0-2 at 3m

GP IIb/IIIa inhibitor NA NA NA 2/2 (100%)

Stenting 1/4 (25%) 6/17 (35%) 25/38 (65%) 2/5 (40%)

Rescue therapy in patients with IST-related occlusion

After EVT (multimodal) Hwang YH et al.

2016

Baek JH et al.

2016

Yoon W et al.

2015

Lee JS et al.

2016

Primary IAT failure 53/208 (25.5%) NA

Adjuvant therapy

GP IIb/IIIa inhibitor 15/20 (67%) 17/53 (32%) None 2/9 (22.2%)

Angioplasty/Stenting 4/20 (20%) 17/45 (38%) 38/40 (95%) 5/9 (56%)

mTICI 2b-3

GP IIb/IIIa inhibitor NA NA NA

Stenting NA 14/17 (83.3%) 36/38 (95%)

mRS 0-2 at 3m

GP IIb/IIIa inhibitor NA NA NA 2/2 (100%)

Stenting 1/4 (25%) 6/17 (35%) 25/38 (65%) 2/5 (40%)

Summary

64/114 (56%)

50/55 (91%)

34/64 (53%)

Rescue therapy in patients with IST-related occlusion

Stent retrieval for ICAS-O. Routine first-

line thrombectomy can effectively

eliminate the major portion of in situ

thrombi.

Endothelial cells are still inflamed and

may cause re-occlusion.

Gp IIb/IIIa inhibitor

Gp IIb/IIIa inhibitor can stabilize the

irritable endothelium.

Angioplasty and stenting can crack the

thrombus and plaque.


Kim BM, J Stroke 2017

Embolic occlusion ICAS-related occlusion

An organized (hard, fibrin-rich) clot is more resilient

and less sticky than fresh (soft, red blood cell-rich)

clots, causing less engagement with an SR and leading

to clot missing during SR therapy

The organized clot may be refractory due to less engagement

with the SR.

If permanent stenting is conducted, the stented artery is likely

more patent as the organized clot is less engaged inside the

stent struts

Kim BM, J Stroke 2017

Possibly atherosclerotic plaque

• Comparison of the efficacy between IA-GP IIb-IIIa inhibitor

and angioplasty and stenting

– Pooled data from 2 stroke centers in S. Korea (CNUH+GUH)

– A; primarily angioplasty and stenting (N=72)

– B; primarily tirofiban IA infusion (N=68)

– Results • A total of 140 patients (median age 67yr, male 65%)

• mTICI 2b-3; 95% (133/140)

• mRS 0-2 at 3m; 60% (84/140)

• mortality; 8%(11/140)

Unpublished data

Center A (N=72) Center B (N=68) P

Rescue therapy Angioplasty and

stenting

IA tirofiban

Procedure time 37.5 (30-48) 53 (36-84) <0.001

Time to reperfusion 275 (205-400) 463 (274-647) <0.001

NIHSS 11 (9-15) 15 (11-20) <0.001

mTICI 2b-3 69 (96%) 64 (94%) 0.71

mRS 0-2 at 3m 41 (57%) 43 (63%) 0.45

Mortality 7 (9.7%) 4 (5.9%) 0.53

Comparison of outcomes of patients from centers A and B.

Unpublished data

Center A (N=72) Center B (N=68) P

Rescue therapy Angioplasty and

stenting

IA tirofiban

Procedure time 37.5 (30-48) 53 (36-84) <0.001

Time to reperfusion 275 (205-400) 463 (274-647) <0.001

NIHSS 11 (9-15) 15 (11-20) <0.001

mTICI 2b-3 69 (96%) 64 (94%) 0.71

mRS 0-2 at 3m 41 (57%) 43 (63%) 0.45

Mortality 7 (9.7%) 4 (5.9%) 0.53

Comparison of outcomes of patients from centers A and B.

Both intracranial angioplasty/stenting and intra-arterial

infusion of a glycoprotein IIb/IIIa inhibitor may be effective and

safe in the treatment of underlying severe ICAS in acute stroke

patients with LVO.

Unpublished data

• Limitations of rescue angioplasty and stenting

– Experienced interventionists

– Neither randomized, nor blinded outcome measurement

– Antiplatelet medication after stenting … ? • Increased risk of bleeding, eg. Intracerebral bleeding

– Branch occlusion during stenting ?

Further study will be warranted…

• Potential therapeutic strategies in ICAS-related occlusion

(+) Significant residual stenosis in the parent artery

A. rush to rescue therapy….

1) Rescue angioplasty/stenting

+/- Glycoprotein IIb-IIIa inhibitor

B. Conservative therapy….

1) IA-glycoprotein IIb-IIIa inhibitor

2) Repeat f/u angiography

(+) reocclusion (-) reocclusion

Primary EVT

Summary

• ICAS-related occlusion may not be uncommon in patients

with acute ischemic stroke with large vessel occlusion

• The potential therapeutic strategies in ICAS-O could be

primarily EVT, but it may not be sufficient to achieve the

substantial reperfusion.

• Further study will be warranted, but based on studies from

Korean researchers, rescue therapy including angioplasty and

stenting or GP inhibitor might be considered.

Thank you for your attention

acute management of stroke due to intracranial...

Documents