Interventional Treatment

of Stroke

Andrew F. Ducruet, MD Barrow Neurological Institute

2018 BNI Stroke Rehab Symposium

October 13, 2018

Disclosures

• Consultant: Medtronic, Penumbra,

Cerenovus

Lecture Overview

• Introduction

• Current State of Interventional

Stroke treatment

• Recent Clinical Studies

• Case Studies

• Future Directions

BNI Endovascular Stroke Volume

Mechanical Thrombectomy:

MERCI

Approved 2004

Aspiration: Penumbra

Approved 2007

First generation IA trials (2013)

No difference in outcomes

Limits of 1st generation IA trials

• Improper patient selection

• Only 47% of patient had baseline CTA or

MRA documenting an occlusion

• Outdated devices incomplete

recanalization

• Only 27% TICI 2B/3

• Significant delays to reperfusion

• Mean 325 minutes in the endovascular cohort

with a strong time-treatment interaction • Every 30 minutes delay 10% worse outcomes

Stentrievers: 2012

IV tPA Primary endpoint Time frame Site of LVO # patients Selection criteria

MR CLEAN 90% mRS at 90 days

< 6 hrs ICA/M1/M2 500 NIHSS > 2

Grey area principle

EXTEND-IA 100%

Reperfusion at 24 hours

without sICH <72 hours

< 6 hrs

ICA/M1/M2

70 Core < 70 cc

Penumbra > 10 cc

REVASCAT 100% mRS 0-2 at 90 days < 8 hrs ICA/M1 206 NIHSS > 5

ASPECT > 6

ESCAPE >70% NIHSS score 0-2 or mRS

0-2 at 90 days

< 12 hrs ICA/M1 314 NIHSS > 5; ASPECT > 5

P2P < 60 min; P2R < 90

min

SWIFT

PRIME

100% mRS at 90 days < 6 hrs ICA/M1 196 ASPECT > 6

NIHSS > 7

2015 Endovascular Stroke Trials

MR CLEAN trial (Netherlands)

– ASPECTS 8-10:

75%

(Berkhemer et al NEJM 2015)

mRS 0-2 at 90d:

- 32.6% vs. 19.1%

- absolute diff: 13.5%

- NNT = 7

EXTEND IA trial (Australia/NZ)

(Campbell et al NEJM 2015)

mRS 0-2 at 90d:

- 71% vs. 40%

- absolute

difference: 31%

- NNT= 3

REVASCAT (Spain)

(Jovin et al NEJM 2015)

mRS 0-2 at 90d:

- 44% vs. 28%

- NNT = 4

- IV tPA failure patients only. (30min

delay in treatment for tPA evaluation)

(Goyal et al NEJM 2015)

mRS 0-2 at 90d:

- 53.0%, vs. 29.3%

- absolute diff: 24%

- NNT = 4

ESCAPE trial (international)

SWIFT PRIME trial (international)

(Saver et al NEJM 2015)

mRS 0-2 at 90d:

- 60% vs. 35%

- NNT = 4

(Goyal et al Lancet 2016)

BNI Vascular Neurology

BESTU: October 2017

Wall Street Journal. 2/6/18

Stroke at the BNI

Positive Endovascular

trials

2011 2015 2014 2013 2012 2017 2016 2019

Negative Endovascular

trials

2018

BESTU

DAWN/

DEFUSE-3

Dr. Waters

Endovascular Stroke

Treatment in 2018:

Techniques

Stentrievers

Trevo Solitaire

Embotrap

3D

Contact Aspiration (ADAPT)

Vargas J, et al. J NeuroIntervent Surg 2017;9:437–441. doi:10.1136/neurintsurg-2015-012211

• SMAT: Stent retriever mediated manual aspiration

thrombectomy

• Tri-axial system: microwire: microcatheter: aspiration

catheter

SMAT (Solumbra)

Recent Endovascular Stroke

Clinical Trials

DAWN Trial

N Engl J Med. 2018 Jan 4;378(1):11-21.

• 500 patients (pivotal); 50 sites

• 6-24 hours

• NIHSS > 9

• ICA or M1 occlusion

• Medical therapy vs. thrombectomy (Trevo)

DAWN Trial

N Engl J Med. 2018 Jan 4;378(1):11-21.

• Clinical Imaging Mismatch (CIM)

• Core defined on DWI or rCBF maps

(RAPID)

• 0-20 cc core & NIHSS >= 10 (≥ 80yr)

• 0-30 cc core & NIHSS >= 10 (< 80yr)

• 31-50 cc core & NIHSS ≥ 20 (< 80yr)

DAWN Trial

N Engl J Med. 2018 Jan 4;378(1):11-21.

3rd European Stroke Organisation Conference (ESOC) 2017. Session PL01. Presented May 16, 2017.

DAWN Trial- RAPID

Primary Outcomes

NNT for functional outcome independence at 90

days= 2.8

* Similar to p<0.0001

N Engl J Med. 2018 Jan 4;378(1):11-21.

DAWN Trial Conclusions

• Thrombectomy associated with higher

functional independence compared to

medical therapy

• Treatment effect size in DAWN is highest

of any stroke trial

• Thrombectomy in patients > 6h showed

comparable safety profile to thrombectomy

performed < 6h

DEFUSE-3

N Engl J Med. 2018 Feb 22;378(8):708-718.

DEFUSE-3 Design

• Age 18-90 years

• ICA or M1 occlusion

• Treatment between 6-16 hours last known

well

• NIHSS ≥6

• Perfusion imaging required

• Initial infarct volume <70cc • Ratio of ischemic tissue to infarct of >1.8

• Absolute value of penumbra of >15cc

• Any FDA-approved thrombectomy device

N Engl J Med. 2018 Feb 22;378(8):708-718.

• Median score on 90 day mRS

• OR favoring endovascular 2.77; P<0.001

Outcome

N Engl J Med. 2018 Feb 22;378(8):708-718.

DEFUSE-3 Findings

• More inclusive than DAWN

• 40% of DEFUSE patients would not

qualify for DAWN

• Larger Core infarcts than DAWN

(70 vs. 50)

• Milder Symptoms (NIHSS ≥ 6)

2018 Guidelines Update

Aspiration vs. Stentriever

• Contact aspiration vs. stentriever

• Randomized, open-label, blinded endpoint trial at 8

centers in France (10/15-10/16)

• 192 randomized to aspiration vs. 189 to

stentriever

• Primary outcome: TICI 2B/3 revascularization • 85.4% in aspiration arm vs. 83.1% in stentriever (p=0.53)

• Secondary outcomes: change in NIHSS at 24h,

mRS at 90 days

• No significant differences

ASTER Trial

• Data presented at 2018 ISC

• 134 patients in aspiration arm, 136 patients in

stentriever arm, 15 centers

• Primary endpoint : mRS = 0-2 at 90 Days

• Secondary endpoints : mRS shift, TICI 2c or 3 within

45 min of groin puncture, time from groin puncture to

TICI 2b/3

• Aspiration was non-inferior • 49% in stentriever vs. 52% in aspiration (P=0.0014)

• 20% in aspiration required stentriever

Aspiration vs. Stentriever

• Available data suggesting no significant

difference between the two techniques

• Aspiration is a reasonable first-line

treatment

The Future

• Larger Core infarcts

• Low NIHSS

What about larger core infarcts?

Only 9% of patients treated had large core (ASPECT 0-5) but no

clear evidence of harm and trend towards benefit

Stroke size and cost: Each additional 1cc of infarct increased hospitalization cost by $122.35

Streib et al (submitted)

Case 1: Large Core Infarct

• 37 year old male last known well 14-16

hours prior to admission, with history of

altercation at a party

• Awoke with right MCA syndrome

• NIHSS = 19

• CTA shows tandem occlusion right

MCA/ICA

CT Head admission

CTA Neck

CTA Head

CT Perfusion

Microcatheter injection

Post-thrombectomy

Post-Thrombectomy MRI

• Showed rapid improvement over next

several days

• Discharged on day 5 intact except

4+/5 in left hand

• Lost to follow-up

Case #1

What about low NIHSS

Stroke. 2011 Nov;42(11):3110-5.

J Neurointerv Surg. 2016 Sep 2 Epub

• NIHSS ≤5

• LVO

• mRS 0-2

• 52 yo male with hypertension

• Onset of facial droop, slurred speech

mild left sided drift at work

• Urgicare ER

• 9.5 hours post-onset

• NIHSS = 4

Case #2: Low NIHSS

Admission MRA

Admission MRI

CT Perfusion

Thrombectomy

Thrombectomy

Post-Thrombectomy

• Immediate improvement of drift and

facial ,speech rapidly normalized

• Discharged home neurologically

intact following workup for AFib

Case #2

• 44 yo otherwise healthy male

• Onset of dizziness, dysphagia,

left facial numbness beginning

on 7/25 in the afternoon

• In the ER, CT head normal,

NIHSS 0.

Case #3:Low NIHSS, Basilar

• Admitted to MGMC due to

difficulty with balance

• MRA and CTA suggestive of

proximal basilar occlusion

Case #3:Low NIHSS, Basilar

• On admission to SJHMC, he has

severe vertigo when sitting up

accompanied by nausea /vomiting,

lateral gaze nystagmus

• NIHSS = 0

Case #3

MRA

Right Subclavian

Right ICA

Left Vertebral

Stentriever Deployed

Left Vertebral post-Thrombectomy

• Symptoms immediately

resolved following

treatment

• MRI shows only

punctate infarcts left

occipital lobe

• Discharged home on

post-procedure day #2

Case #3

Future Directions

• IN EXTREMIS: Montpelier

• Clinically severe stroke and

ASPECTS 0-5

• Low NIHSS (<6) and M1 occlusion

Thank You!

andrew.ducruet@barrowbrainandspine.com