Endovascular Neurointervention

in Cerebral Ischemia

Beyond Thrombolytics

Curtis A. Given II, MD

Co-Director, Neurointerventional Services

Baptist Physician Lexington

72 y/o female with a recent diagnosis of

paroxysmal atrial fibrillation developed

right hemiparesis and global aphasia

while at interstate “rest stop”. Patient

was taken to regional medical facility

(Corbin Baptist Regional) within 1 ½

hours of onset of symptoms.

NIHSS was 16 and head CT was

normal. IV-tPA was administered by the

Emergency room physician and the

patient was transferred to UK.

Upon arrival to UK, the patient was

hemiplegic with global aphasia and

NIHSS was 22. Repeat head CT was

normal. Patient was immediately taken

to the Angiography suite

First pass with Merci retriever was performed at approximately 6 hours

after the onset of symptoms

Two passes of the Merci retriever resultant in complete recanalization

of the left middle cerebral artery

The patient began to have purposeful movement of her right arm and leg

Immediately after the procedure. MRI of the head on the following day revealed

only a few small infarcts. She was discharged home, independent and without the

need for rehabilitation, and an NIHSS of 0.

Stroke • Impact

– Every 45 seconds someone in the U.S. has a stroke

– Stroke is #3 cause of death

– Stroke is #1 cause of adult disability

– Approximately 87% ischemic

• Limited treatment options

– Intravenous lytic

• Limitation: must be administered within 3 hours of stroke

onset

• Estimated <5% of stroke patients receive IV lytic

– Mechanical revascularization with Merci® and Penumbra ®

Retrieval Systems

• Option beyond 3 hour window, and for patients who are

ineligible for or who fail IV t-PA therapy

Time Window for Potential Stroke

Treatments

Time Window 0-4.5 hrs 0-6 hrs >6 hrs ‡

Options • IV tPA

• Merci*

• Penumbra*

•Solitaire

• Merci

• Penumbra

•Solitaire

• IA Lytic†

• Merci

• Penumbra

•Solitaire

* 0-3 hours in patients who are contraindicated for IV tPA or who fail IV tPA therapy.

† Not FDA approved.

‡ The MERCI and Multi MERCI trials evaluated patients up to 8 hours

Patient Selection for Intra-arterial Therapy

Generally patients with symptoms of large

vessel occlusion (NIHSS > 8)

No changes of large infarct (less than 1/3 of vascular territory) on CT or DWI

No hemorrhage on CT

< 8 hours since “last seen normal” OR significant tissue “at-risk/penumbra” on Perfusion imaging

Any patient with basilar occlusion

Large vessel occlusion on CTA/MRA

Contraindications to IA Thrombolysis

• CT-documented hemorrhage or significant mass effect

• Fibrinogen < 120 mg*

• Platelet count < 80,000*

• Active internal bleeding or recent surgery (<10 days)*

• Prior allergic reaction to r-tPA*

• BP > 200 systolic or >120 diastolic despite medical therapy

• No clot on angiography

* Not contraindication to mechanical thrombectomy

What about patients presenting after 8

hours or “wake up” strokes?

• Significant problem,

particularly in patients with

an unknown time to onset

(“wake up” strokes).

• Traditionally, these

patients offered only

supportive measures

• 50% of patients may have

a persistent ischemic

penumbra at 24 hrs.

Slide borrowed from Dr. Lev’s ASNR presentation 2008

rCBF 60% rCBV 110%

TTP > 6 sec

Trials of Intra-arterial Thrombolytic Agents

PROACT II Furlan A. et al. JAMA 282:2003, 1999

• Randomized open-label trial of prourokinase (r-pro-UK) 9 mg

with heparin vs systemic heparin in patients with middle

cerebral artery occlusions within 6 hours of onset.

• Pro-urokinase delivered over 2 hours by microcatheter into

the middle cerebral artery at the face of the clot.

• Mechanical clot disruption was not permitted.

• Final angiogram at 2 hours in both groups.

Pre Post – 20 mg IA r-tPA Interim

Endovascular Thrombectomy of Cerebral Vessels

• Merci Retriever

• First surgical device

cleared by the FDA for acute

ischemic stroke patients

• Restores blood flow to the

brain by physically removing

thrombus from the occluded

precerebral or cerebral

vessel

Candidates for Merci Therapy

• Patients who are ineligible for treatment with intravenous tPA :

– outside 3-4.5 hour window

– other clinical factors, eg. recent surgery,

long-term current use of anticoagulants for atrial

fibrillation, allergy to t-PA

• Patients who have failed (or not responding to) prior

intravenous t-PA therapy

Only used for patients with ischemic stroke, not hemorrhagic stroke

Specialized Devices

• Merci® Retriever

• Merci® Microcatheter

• Merci® Balloon Guide Catheter

Endovascular thrombectomy devices were

cleared by the FDA in August 2004

Merci Registry Background

The Merci Registry is a Post-Market study

designed to capture “real-world”

interventional treatment of acute stroke with

the Merci Retriever system, unconstrained

from the “trial” environment

The Largest, Prospective Multi-Center Study of

Mechanical Embolectomy for AIS

• Prospective, multi-center study (36 centers)

• 1,000 patients enrolled in 3 years

– Interim results presented at ISC 2010 analyzed 625 patients

• Inclusion criteria: procedure must have included a Merci

Retriever and patient informed consent

• No exclusion criteria

• Interim results validated MERCI and Multi MERCI results

in a much larger unconstrained cohort

Merci Registry

Revasc Rates by Final TICI Score Merci Registry – Interim Analysis

Good Outcomes by Final TICI Score Merci Registry – Interim Analysis

Good Outcomes defined as mRS=0-2 at 90 days

The Penumbra System is designed to revascularize

large vessel occlusions in the intracranial circulation. The

Penumbra System uses a unique microcatheter and

SeparatorTM based thrombus debulking approach to

intracranial vessel revascularization.

The Penumbra advantages are:

•Proximal working position

•Continuous Aspiration

•Variable sizing for variable anatomy

Penumbra Thrombectomy System

So What’s Next?

• “Stent-trievers”

• Solitaire® and Trevo®

• Allow for faster and higher

recanalization rates, with

fewer device deployments

(‘passes’), and improved

clinical outcomes relative to

Merci Trevo™

Retrieve with

Confidence

Merci Retriever ® Clinical History

The Solitaire™ FR device Retrospective data demonstrates higher angiographic and neurological outcomes when compared to these Merci® registries.

**TICI 2a-3 classification was used

Merci® Competitive Messages:

1. 2.5x improvement in Recanalization 2. 1.7x improvement in neurological outcomes 3. 55% reduction in mortality

Solitaire™ FR revascularization device vs. The

Concentric ® Merci® Retriever1 (SWIFT Study)

(Core Lab)

79 yo WM awoke and walked to bathroom at 9am, wife heard loud noise and went to find

husband lying in the floor of bathroom, aphasic and right sided hemiplegic. Transferred to

CBH and received full-dose tPA at 12pm (approx. 3hrs after symptom onset). Initial NIHSS

was 24 upon arrival to CBH. CT Perfusion scan shows large area of ischemia in left MCA

territory consistent with large vessel occlusion, sent for possible thrombectomy.

Partial flow restoration with Solitaire at

130pm (4.5 hrs after sx onset)

Two passes with 4x20mm Solitaire

The next day, the patient had regained anti-gravity strength in the right upper and

lower extremities and significant improvement in speech (mild-moderate residual

expressive aphasia). 24 hr NIHSS had improved to 6 (initial was 24).

TTD rCBV 24 hr CT

TREVO 2 Thrombectomy REvascularization of large Vessel Occlusions

in acute ischemic stroke

Randomized, prospectively controlled, multi-center, non-inferiority IDE study of arterial revascularization in acute ischemic stroke patients

Up to 25 sites (at least 20 sites in North America) – 1st and only site in Kentucky

178 patients, with a planned interim analysis at 120

Randomized 1:1, with test arm using the Trevo device, the control arm using the Merci device

TTD

“time-to-drain”

TTD

“time-to-drain” TTD

“time-to-drain”

rCBV

“relative cerebral

blood volume”

rCBV

“relative cerebral

blood volume”

rCBV

“relative cerebral

blood volume”

27 yo male with history of eosinophilic

myocarditis and dilated cardiomyopathy,

presented with acute onset of left facial droop,

left hemiplegia, dysarthria and gaze defect.

Initial NIHSS=16. He was antiocoagulated for

his cardiomyopathy and prior stroke (prior full

recovery) with a PT/INR or 26.7/2.3

(therapeutic anticoagulation).

Given anticoagulation, he was not a candidate

for thrombolytic therapy (tPA). Was evaluated

and treated my partner Christian Ramsey.

TTD

“time-to-drain”

TTD

“time-to-drain” TTD

“time-to-drain”

rCBV

“relative cerebral

blood volume”

rCBV

“relative cerebral

blood volume”

rCBV

“relative cerebral

blood volume”

4x20mm Solitaire

The next day, the patient had regained full strength in the left upper and lower

extremities and with only minimal residual facial droop. 24 hr NIHSS had improved

to 1 (initial was 16).

TTD

“time-to-drain”

57 yo BF with “wake up” stroke manifesting as slurred speech and right arm/leg paralysis,

resulting in fall to floor upon getting out of bed. PMH significant for non-ischemic cardiomyopathy

with pacemaker (EF 30-35%), type II DM, and dyslipidemia (not on statin therapy). Initial NIHSS

was 8 in the ED, and was NIHSS of 11 prior to procedure.

rCBV

“relative cerebral blood volume”

4 passes with the

Solitaire and 6mg of IA

tPA into the left MCA

TTD

Initial CT Perfusion

TTD

F/u CT Perfusion 3 days later

At the time of transfer to rehab, she regained full strength in her right lower extremity and her

speech had significantly improved. Unfortunately she was still plegic in the right upper extremity.

334 patients received “endovascular” therapy after IV t-PA administration (11 patients did not receive angiogram, 89 patients endovascular therapy was not administered).

142 patients received “standard” therapy consisting of additional IA t-PA 42.5% of patients in the “endovascular” arm received intra-arterial t-PA as MONO THERAPY.

22 patients - EKOS cath and t-PA

95 patients – Merci (57 got additional IA t-PA)

54 patients – Penumbra (38 got additional IA t-PA)

5 patients – Solitaire (2 got additional IA t-PA) ONLY 1.5% of patients in the “endovascular” received most current treatment.

16 patients – “other” (9 got additional IA t-PA) not specified as to what “other” is

“Endovascular” Treatment

181 patients, 163 patients completed (18 excluded – lack of occlusion, clinical improvement, etc.)

Median time to treat 3.75 hrs

109 patients (67%) received intra-arterial t-PA as MONO THERAPY (0.9mg/kg given over 1hr, median dose 40mg)

ONLY 56 patients (33%) received adjunctive mechanical thrombectomy

23 stent-treivers ------- ONLY 14 % of the “endovascular” arm received current treatment

18 Solitaire

5 Trevo

5 Merci

9 Penumbra

Remainder of devices not specified in the article.

In the 2 “landmark” trials assessing “endovascular” stroke therapy recently published

Only 28 patients (5.4%) of the endovascular arm were treated with “current” technology (i.e. stent-trievers)

63% of patients receiving “endovascular” therapy received only IA tPA therapy (no mechanical thrombectomy of any method, i.e. no Merci, no Penumbra, no stent-triever)

In my opinion, these trials were largely a revisit of the PROACT trials circa 1998.

CBH is one of 20-25 sites that are conducting a prospective randomized trial comparing IV tPA versus IV tPA and Solitaire in the treatment of large vessel occlusions and acute stroke.

• Presented to CBH ED and received IV tPA (bolus at 1:30 am, 2.5 hrs

after sx onset)

• Initial NIHSS was 17

4/26/11

• 62 yo WF with history of CHF (20-25% EF), Cardiomyopathy,

COPD, and recent ablation

• Normal state of health until 11pm, when she sustained a witnessed

fall, with acute onset of aphasia and right sided hemiplegia

Right CCA Left CCA

Only mild clinical improvement (NIHSS 15),

brought to cath lab, initial angios at 2:30am

Right CCA

Left CCA

Left VA

Left ICA with occluded left MCA

s/p aspiration thrombectomy with

9F Concentric Balloon catheter

Carotid Wallstent, effectively

(luckily) trapped residual clot

against ECA origin, protecting the

CCA/ICA

Opening flow to ICA, allowed for

tPA to reach intracranial

circulation, and natural lysis of

clot. No further intervention done.

She regained full strength in

the right side of her body and

had only expressive aphasia

on 4/27/11. She began to

recover speech on 4/28/11,

and was left with only a mild

aphasia

4/27/11

2002 2006

Be Proactive You do not have to wait for the stroke

Conclusion

Evolving field with new technologies

allowing us to extend the therapeutic window

well beyond 3 hours

Perfusion imaging will likely triage patient

care in future

Future (? current) standard of care likely to

involve a combination of IV and

Endovascular therapies