1. Interventional Stroke Treatment 2015
Sudipta Roychowdhury, MD
Director of Interventional Neuroradiology
Director of Magnetic Resonance Imaging
Clinical Associate Professor of Radiology
Rutgers-RWJ Medical School
University Radiology Group

2. Stroke Therapy Timeline
MR CLEAN
SWIFT PRIME EXTEND IA
ESCAPE
REVASCAT
THERAPY
Solitaire
Penumbra
Trevo
PROACT II
IA tPA
Angioplasty
Stenting
Level I
Evidence
Bridging IV/IA
IV tPA
MERCI
ACE
IV tPA (4.5h)
Generation 1
Generation 2
Generation 3
1995
2000
2005
2010
2015
FDA Approved - Yellow
Off-label - Red

3. Ischemic Stroke Interventions
Ischemic Stroke Therapy
FDA
Small Series
Large Trial Efficacy
IV t-PA
Yes
IA t-PA No
IV and IA t-PA
MERCI Device
Penumbra Device
Solitaire Device
Trevo Device
Angioplasty/Stenting 3

4. NINDS tPA Trial NINDS tPA trial (1995) Benefit still seen 3-4.5 hours
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 hours
NEJM 9/2008 European study

5. 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

6. Case
55 y/o M presents after 5 hours of onset of rapidly progressive quadriparesis, ataxia, and dysphagia.
Head CT was normal.

7. Basilar Artery Occlusion

8. Basilar Angioplasty and Thrombolysis IA t-PA

9. Excellent Recanalization and Excellent Outcome

10. 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.

11. Basilar Artery Occlusion

12. Basilar Angioplasty/Stent & Thrombolysis IA t-PA

13. Futile Recanalization

14. MERCI Device
MERCI 14

15. 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

16. 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!

17. 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. MD, FRACP; Davis, Stephen M. MD, FRACP
Stroke Volume 37(5), May 2006, pp

18. 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 18

19. Case
38 y/o F presents with acute left sided hemiplegia presents at 4 hours. History of atrial fibrillation.
Head CT was unremarkable.

20. MERCI

21. Penumbra Device
Suction catheter with separator wire which prevents thrombus from clogging the tip 21

22. 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

23. Case
44 y/o M presents with mental status changes and left leg weakness at 6 hours.
Head CT was unremarkable.

24. Penumbra ACA Infarct

25. Stent Retrievers 3rd Generation endovascular stroke treatment
Immediate flow restoration
Trap thrombus within stent struts and retrieved
Removable device so no anti-platelets needed
Solitaire
Trevo

26. Solitaire

27. 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

28. Case
65 y/o M presents acute left sided hemiplegia at 4 hours and was on Coumadin for atrial fibrillation.
Head CT was unremarkable.

29. Solitaire

30. Trevo Trevo was significantly better than Merci
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

31. Futile Recanalization
Unfavorable outcome even with excellent endovascular recanalization

32. 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

33. 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

34. 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

35. 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

36. 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)
PWI (Penumbra)

37. 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

38. Case 6
76 y/o F noted to have left arm/leg weakness 2 days after pelvic surgery. 38

39. Core: MR Diffusion MR Diffusion: less than 1/3 MCA core infarct
Head CT
MR Diffusion
CTA – R M1 occlusion
MR Diffusion: less than 1/3 MCA core infarct

40. CT Perfusion and MR Diffusion
CBF
TTP (Penumbra)
Diffusion (Core) 40

41. Penumbra Device 41

42. CT Perfusion after Penumbra Thrombectomy
TTP
TTP after
thrombectomy
Diffusion 42

43. 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 43

44. 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 44

45. Level I Interventional Evidence
MR CLEAN
ESCAPE
EXTEND-IA
SWIFT PRIME
REVASCAT
(THERAPY)

46. 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

47. MR CLEAN mRS mRS (Modified Rankin Scale) 0 – No symptoms
1 – No significant disability
2 – Slight disability
3 – Moderate disability
4 – Moderate severe disability
5 – Severe disability
6 – Death

48. MR CLEAN Study Conclusion
4/21/2017 1:43 PM
MR CLEAN Study Conclusion
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
Add your key takeaways / perspective
O.A. Berkhemer et. al. A Randomized Trial for Intraarterial Treatment for Acute Ischemic Stroke. N Eng J Med December 2014. V4

49. Merci Retriever®, EKOS, IA Lytic, Penumbra 24% pen (n=34) 27% nonp
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% ICA
44% M1
44% M2
23% multi M2
40.8%
(N=415)
38.7%
(N=214)
MR RESCUE
Merci Retriever®, EKOS, IA Lytic, Penumbra
24% pen
(n=34)
27% nonp
(n=30)
21% pen (n=34)
17% nonp
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
86.2%
(n=29)
71%
(n=35)
40%
REVASCAT
ASPECTS
66%
(n=102)
44%
28%
(n=103)
THERAPY
CTA clot >8mm
100% Penumbra
38%
(n=50)
30%
(n=46)

50. 4/21/2017 1:43 PM
What does this mean?
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.
Add your key takeaways / perspective V4

51. 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. 51

52. 38 y/o Comatose F
Angiogram at 36 hrs 52

53. Basilar Artery Angioplasty and Thrombolysis at 36 Hours53

54. 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…” 54

55. Interventional Stroke Treatment 2015
Sudipta Roychowdhury, MD
Director of Interventional Neuroradiology
Director of Magnetic Resonance Imaging
Clinical Associate Professor of Radiology
Rutgers-RWJ Medical School
University Radiology Group

56. Stroke Therapy Timeline
MR CLEAN
SWIFT PRIME EXTEND IA
ESCAPE
REVASCAT
THERAPY
Solitaire
Penumbra
Trevo
PROACT II
IA tPA
Angioplasty
Stenting
Level I
Evidence
Bridging IV/IA
IV tPA
MERCI
ACE
IV tPA (4.5h)
Generation 1
Generation 2
Generation 3
1995
2000
2005
2010
2015
FDA Approved - Yellow
Off-label - Red