Interventional Stroke Treatment 2015

Sudipta Roychowdhury, MD

Director of Interventional NeuroradiologyDirector of Magnetic Resonance ImagingClinical Associate Professor of Radiology

Rutgers-RWJ Medical SchoolUniversity Radiology Group

Stroke Therapy Timeline

19951995 20002000 20052005 20102010

IV tPA IV tPA MERCIMERCIPROACT IIPROACT II

IA tPAIA tPA

PenumbraPenumbra

ACEACE

SolitaireSolitaire

IV tPA (4.5h)IV tPA (4.5h)

AngioplastyAngioplastyStentingStenting

Generation 1Generation 1 Generation 3Generation 3Generation 2Generation 2

Off-label - RedOff-label - RedFDA Approved - Yellow FDA Approved - Yellow

Bridging IV/IABridging IV/IA TrevoTrevo

20152015

Level I Level I EvidenceEvidence

MR CLEANMR CLEANSWIFT PRIMESWIFT PRIME

EXTEND IAEXTEND IAESCAPEESCAPE

REVASCATREVASCATTHERAPYTHERAPY

Ischemic Stroke Therapy FDA Small Series Large Trial Efficacy

IV t-PA Yes Yes Yes

IA t-PA No Yes No

IV and IA t-PA No Yes No

MERCI Device Yes Yes No

Penumbra Device Yes Yes Yes

Solitaire Device Yes Yes Yes

Trevo Device Yes Yes Yes

Angioplasty/Stenting No Yes No

Ischemic Stroke Interventions

NINDS tPA Trial• NINDS tPA trial (1995)

– IV tPA vs Placebo < 3hrs– Outcomes improved with all 4 outcomes

Symptomatic hemorrhage 6.4% vs 0.6%– Mortality 17% vs 21% placebo at 3 months– Established IV tPA as gold standard < 3hrs– Better for small rather than large occlusions

• Benefit still seen 3-4.5 hours NEJM 9/2008 European study

PROACT II

• PROACT II (1998) – Dr. Irwin Keller NJ Investigator

– IA Prourokinase < 6 hrs– Favorable outcome 40% vs 25% control– Recanalization 66% vs 13% control– Mortality 25% vs 27% control– Symptomatic hemorrhage 10% vs 2% control– IA Prourokinase and tPA not FDA approved

Case

• 55 y/o M presents after 5 hours of onset of rapidly progressive quadriparesis, ataxia, and dysphagia.

• Head CT was normal.

Basilar Artery Occlusion Basilar Artery Occlusion

Basilar Angioplasty and Thrombolysis IA t-PA

Excellent Recanalization and Excellent Outcome

Case

• 77 y/o F presents after 4 hours of onset of slurred speech and ataxia rapidly progressing to loss of consciousness

• Head CT was unremarkable.

Basilar Artery Occlusion

Basilar Angioplasty/Stent & Thrombolysis IA t-PA

Futile Recanalization

MERCI Device

MERCIMERCI

MERCI Trial• MERCI (2005)

– MERCI < 8 hrs; n=141; No control arm– Recanalization 46% (66% PROACT II)– Mortality 44% (25% PROACT II, 27% Control)– Symptomatic hemorrhage 7.8%– Primary outcome recanalization not outcome– Results worse than PROACT II– FDA approved but heavily criticized for

approval before establishing efficacy

Multi-MERCI Trial

• Multi- MERCI (2006) – MERCI +/- IV tPA < 8 hrs; n=164; No control– Recanalization 54% and 69% w IA tPA– Mortality 31%; Symptomatic hemorrhage 9%– Primary outcome recanalization not outcome– Results still worse than PROACT II– Still trying to establish efficacy after FDA

approval!

Does the MERCI Device Work?• “In summary, the MERCI study does not provide

any evidence of improved outcomes or greater recanalization rates…. In addition, both clinically significant complications and mortality are higher than the results of other interventional trials…. the results do not support the proposal that the Merci retrieval device works by any definition.”

Wechsler, Lawrence R. MD, Donnan, Geoffrey A. Wechsler, Lawrence R. MD, Donnan, Geoffrey A. MD, FRACP; Davis, Stephen M. MD, FRACPMD, FRACP; Davis, Stephen M. MD, FRACPStroke Volume 37(5), May 2006, pp 1341-1342 Stroke Volume 37(5), May 2006, pp 1341-1342

MERCI: Defended

• Why high recanalization but not better outcomes?

• Comparing MERCI to PROACT II• Different pt selection – MERCI trials included pts

with poor functional status unlike PROACT II• If adjust for patient selection, similar mortality

and outcome

Case

• 38 y/o F presents with acute left sided hemiplegia presents at 4 hours. History of atrial fibrillation.

• Head CT was unremarkable.

MERCI

Penumbra Device

Suction catheter with separator wire which Suction catheter with separator wire which prevents thrombus from clogging the tipprevents thrombus from clogging the tip

Penumbra Trial

• Penumbra – n=125; Recanalization 82% (PROACT II 66%) – Mortality 32% (25% PROACT II, 27% Control)– Symptomatic hemorrhage 11%– Primary outcome recanalization – 36% good outcome; No control arm– 510k FDA approval – “equivalent” to MERCI

Case

• 44 y/o M presents with mental status changes and left leg weakness at 6 hours.

• Head CT was unremarkable.

Penumbra ACA Infarct

Stent Retrievers

• 3rd Generation endovascular stroke treatment• Immediate flow restoration• Trap thrombus within stent struts and retrieved• Removable device so no anti-platelets needed

TrevoTrevo

SolitaireSolitaire

Solitaire

Solitaire – SWIFT Trial

• SWIFT (SOLITAIRE With the Intention for Thrombectomy) • Solitaire (S) versus Merci (M) randomized trial 200 intended pts but

stopped at 144 by safety board• Successful recanalization without symptomatic hemorrhage –

occurred in 61% of the Solitaire group and 24% of the Merci group. Highly significant difference with a P value of .0001

• Symptomatic intracranial hemorrhage (2% S vs. 11% M). • All intracranial hemorrhage (17% S vs. 38% M). • Good 90-day neurologic outcome (58% S vs. 33% M). • 90-day mortality (17% S vs. 38% M).

• Solitaire was significantly better than Merci

Case

• 65 y/o M presents acute left sided hemiplegia at 4 hours and was on Coumadin for atrial fibrillation.

• Head CT was unremarkable.

Solitaire

Trevo

• Trevo 2 Trial : Trevo versus Merci retrievers for large vessel stroke

• Randomized Trevo Retriever group 88 patients and Merci Retriever group 90 pts

• 76 (86%) patients in the Trevo group and 54 (60%) in the Merci group met the primary endpoint after the assigned device. p<0·0001).

• Incidence of the primary safety endpoint did not differ between groups (13 [15%] patients in the Trevo group vs 21 [23%] in the Merci group; p=0·1826).

• Trevo was significantly better than Merci

Futile RecanalizationUnfavorable outcome even with excellent

endovascular recanalization

How do we select Stroke Patients to avoid Futile Recanalization?

• Time versus Penumbra versus Core • Time

– Less than 6 hours for IA tPA (Anterior)– Less than 8 hours for mechanical (Anterior)– Unknown time for posterior circulation

• Penumbra – Potential stroke territory– CT perfusion – very controversial

– Not accurate predictor of penumbra– High radiation dose– Fallen out of favor by MGH original CTP advocates

– Delayed CTA images for collaterals

How do we select Interventional Ischemic Stroke Patients?

• Core – Actual irreversibly infarcted brain tissue– If less than 1/3 of MCA territory has been infarcted,

better chance for good outcome with recanalization– If the Core is smaller with larger penumbra, the

patient may have good collaterals which will allow better outcome with recanalization.

• ASPECTS criteria• MRI diffusion

ASPECTS Criteria

• Alberta Stroke Program Early CT score (ASPECTS) is a 10-point CT scan score

• ASPECTS predicts core of infarct• A normal CT scan receives ASPECTS of 10 points.  • To compute the ASPECTS, 1 point is subtracted from 10

for any evidence of early ischemic change for each of the defined regions OF MCA territory

• A score of 0 indicates diffuse involvement throughout the MCA territory 

• Patients with ASPECTS score of 8-10 had better outcomes than patients with 7 or less at both shorter (less 5 hours ) and longer (greater than 5 hours) recanalization

ASPECTS Criteria

• A normal CT scan receives ASPECTS of 10 points.  • To compute the ASPECTS, 1 point is subtracted from 10

for any evidence of early ischemic change for each of the defined regions OF MCA territory

MR Diffusion Criteria

• MR diffusion accurately predicts core of infarct• If less than 1/3 MCA territory or less than 70ml volume,

better outcome endovascular treatment (Volume = ABC/2)• If brainstem infarcted in posterior circulation, poor outcome

with basilar stroke.• Takes additional time to obtain MR diffusion

Diffusion (Core)Diffusion (Core) PWI (Penumbra)PWI (Penumbra)

TICI Criteria for M1 Occlusion

• Grade 0 – No antegrade flow beyond occlusion

• Grade 1 – Open beyond obstruction but not

distal• Grade 2a – Less 50% MCA

circulation• Grade 2b – Greater than

50% MCA circulation• Grade 3 – Entire MCA

circulation open

• Grade 2B and 3 – Best neurological outcomes

Case 6

• 76 y/o F noted to have left arm/leg weakness 2 days after pelvic surgery.

Core: MR Diffusion

MR Diffusion: less than 1/3 MCA core infarctMR Diffusion: less than 1/3 MCA core infarct

MR DiffusionMR DiffusionHead CTHead CT CTA – R M1 occlusionCTA – R M1 occlusion

CT Perfusion and MR Diffusion

Diffusion (Core)Diffusion (Core)TTP (Penumbra)TTP (Penumbra)CBF CBF

Penumbra Device

CT Perfusion after Penumbra Thrombectomy

DiffusionDiffusionTTP after TTP after thrombectomythrombectomy

TTPTTP

IMS III (2008-2012)

• Interventional Management of Stroke III

• NEJM March 2013 results – IV tPA only vs IV + IA tPA / Mechanical

– Trial stopped in 2012 as ongoing data could not show benefit of combined IV+ IA superior to IV tPA alone

– No distinction between small and large vessel strokes– Large vessel occlusions did better with IA– Limited by older endovascular devices– No CTA, No ASPECTS criteria

SYNTHESIS Expansion Trials

• NEJM March 2013– IV tPA only <3 hrs vs Combined IV + IA tPA and/or

Mechanical Device < 6hrs– Can we do better than IV tPA?– Endocvascular Tx: Catheter & wire, Merci and

Penumbra, minimal Stent-Retrievers– Limited by older endovascular devices– No difference in outcomes– No distinction between large and small vessel strokes

Level I Interventional Evidence

• MR CLEAN• ESCAPE

• EXTEND-IA• SWIFT PRIME• REVASCAT• (THERAPY)

MR CLEAN Study Details

• Control – IV/Medical only versus Interventional arm - IA and IV• MR CLEAN demonstrated a 71% improvement in good neurological

outcomes for Interventional compared to medical management/TPA (32.6% (76/233) vs. 19.1% (51/267))

• There was no safety difference in adverse events (47% vs. 42%) , ICH (7.8% vs. 6.4%) or 90 day mortality (21% vs 22%) between the two groups.

• Lower absolute rates of 90day mRS 0-2 and higher complication rates seen in MR CLEAN vs. prior studies reflect the ‘real-world’ experience in the Netherlands, particularly the relatively high rate of ICA lesions vs. prior studies like IMS3 (26% vs. 15%)

• Stent Retrievers used in 97% of interventions• There was a improved mRS shift for Interventional vs Control• First large scale study demonstrating interventional superiority

||

MR CLEAN mRS

mRS (Modified Rankin Scale)mRS (Modified Rankin Scale)

0 – No symptoms0 – No symptoms1 – No significant disability1 – No significant disability2 – Slight disability2 – Slight disability3 – Moderate disability3 – Moderate disability4 – Moderate severe disability4 – Moderate severe disability5 – Severe disability5 – Severe disability6 – Death6 – Death

• In patients with acute ischemic stroke caused by a large

arterial occlusion of the anterior circulation, intraarterial

treatment within 6 hours was effective and safe

• IA treatment leads to a clinically significant increase in the

functional independence in daily life by 3 months, without an

increase in mortality

• Triggered stoppage of multiple other trials: ESCAPE, SWIFT

PRIME, Extend IA, REVASCAT, and THERAPY

MR CLEAN Study Conclusion

O.A. Berkhemer et. al. A Randomized Trial for Intraarterial Treatment for Acute Ischemic O.A. Berkhemer et. al. A Randomized Trial for Intraarterial Treatment for Acute Ischemic Stroke. N Eng J Med December 2014.Stroke. N Eng J Med December 2014.

Trial

Imaging Required to Confirm Occlusion

Prior to Randomization?

Device(s) Used in Intervention Arm

TICI 2b/3 Revascularization

Rate in the Intervention Arm

mRS 0-2

Intervention Arm Control Arm

IMS III No

IA Lytic (138), Merci Retriever® (95), EKOS (22), Penumbra (54), Solitaire FR (5)

38% ICA44% M144% M2

23% multi M2

40.8%(N=415)

38.7%(N=214)

MR RESCUE No Merci Retriever®, EKOS, IA Lytic, Penumbra

24% pen(n=34)

27% nonp(n=30)

21% pen (n=34)

17% nonp(n=30)

26% pen (n=34)

10% nonp(n=20)

MR CLEAN Head CT 97% Stent Retrievers, 2% other Mechanical

58.7% (N=196)

33% (N=233)

19% (N=267)

ESCAPE CTA Collaterals, ASPECTS 86% Stent Retriever 72.4%

(n=156)53.0%

(n=164)29.3%

(n=147)

SWIFT PRIME CTP 100% Stent Retriever 88.0%(n=83)

60.2%(n=98)

35.5%(n=93)

EXTEND-IA CTP 100% Stent Retriever 86.2%(n=29)

71%(n=35)

40%(n=35)

REVASCAT ASPECTS 100% Stent Retriever 66%(n=102)

44%(n=102)

28%(n=103)

THERAPY CTA clot >8mm 100% Penumbra 38%(n=50)

30%(n=46)

• Interventional therapy (with IV tPA) may have become the

gold standard for large vessel ischemic stroke in 2015.

– MR CLEAN, ESCAPE, SWIFT PRIME, REVASCAT, EXTEND-IA, THERAPY

• However, the selection criteria for interventional stroke

treatment is not uniform.

– Head CT, ASPECTS, Diffusion MRI, CTA, Delayed CTA, CTP

• Medicolegal Implications: Large vessel ischemic stroke

patients may need to have rapid access to Interventional tx.

What does this mean?

Case

• 38 F who is 16 weeks pregnant presented with slurred speech and facial weakness to the ER after 8 hours. She became comatose after 24 hours after admission. MRI performed at 30 hours. Angiogram performed at 36 hours after emergency hospital privileges.

38 y/o Comatose F

Angiogram at 36 hrsAngiogram at 36 hrs

Basilar Artery Angioplasty and Thrombolysis at 36 Hours

Ischemic Stroke Treatment Guidelines

• IV tPA (<4.5 hours) • Add Interventional (IA) treatment if:

– Do CTA if MCA syndrome or NIHSS > 7– CTA shows large vessel occlusion– Patient not a IV t-PA candidate – Patient not improving with IV t-PA– ASPECTS criteria 8-10 for MCA stroke– MR diffusion shows small or no core infarct

• Transfer to comprehensive stroke center if large vessel stroke

• Need to await further results of trials• “Do no harm…”

Interventional Stroke Treatment 2015

Sudipta Roychowdhury, MD

Director of Interventional NeuroradiologyDirector of Magnetic Resonance ImagingClinical Associate Professor of Radiology

Rutgers-RWJ Medical SchoolUniversity Radiology Group

Stroke Therapy Timeline

19951995 20002000 20052005 20102010

IV tPA IV tPA MERCIMERCIPROACT IIPROACT II

IA tPAIA tPA

PenumbraPenumbra

ACEACE

SolitaireSolitaire

IV tPA (4.5h)IV tPA (4.5h)

AngioplastyAngioplastyStentingStenting

Generation 1Generation 1 Generation 3Generation 3Generation 2Generation 2

Off-label - RedOff-label - RedFDA Approved - Yellow FDA Approved - Yellow

Bridging IV/IABridging IV/IA TrevoTrevo

20152015

Level I Level I EvidenceEvidence

MR CLEANMR CLEANSWIFT PRIMESWIFT PRIME

EXTEND IAEXTEND IAESCAPEESCAPE

REVASCATREVASCATTHERAPYTHERAPY