Recent evidence for mechanical thrombolysis

1. VIPUL GUPTA
NEUROINTERVENTION SURGERY, MEDANTA THE MEDICITY

2. 0
10
20
30
min
CBF(ml/100g/min)
300 9060 4120 5 6 24 48h
Infarct-
threshold
Penumbra
Vital tissue
InfarctSingle cell
necrosis
3

3. Less than 10% patients are eligible

4. ECASS 3
52.4% vs. 45.2%; OR, 1.34; 95% CI,1.02 to 1.76; P=0.04.
IV tPA beyond 3-hours….

5. 3- 6 hours
PWI/ DWI > 1.2
Non significant
difference in
good outcome

7. • 53 studies, 2066 patients
• Sp.- 24%, IV tPA- 46%, IA- 64%, Mechanical- 84%
• Good outcome more in recanalized patients (OR- 4.4)
• Less mortality in recanalized patients

8. •Distal MCA – 44%
•Proximal MCA - 30%
•Terminal ICA - 6%
•Tandem cervical ICA/MCA
-27%
•Basilar artery- 30%

10.  IV-tPA given in MVO- but not effective-
(bridging)
 IV-tPA not possible-( >4.5 hrs, wake-up
strokes, anti-coagulants, recent surgery etc. )
(and MVO)

12.  21 sites- 8-years- 127 patients
 Revascularization in 67%, seventeen
procedural complications
 Mostly used MERCI device- first
generation;
 Trial completed over 8-years !!!
Time to groin puncture was 6 hrs 21 min !!!
Imaging to puncture- 2hrs 4min !!!

14. Intra-arterial methods
• IA-tPA- 71% (51)
• Microsonic – 71% SV Infusion with
tPA (14)
• Merci- 73% (77)
• Penumbra- 85% (39)
• Solitaire- 75% (4)- used in 1.6%
Rapidity of treatment
• IMS 1 and II trials, 30-minute delay
– 10% less probability of independent
existence
• Delay in IMS III was 32 min longer
than IMS I study
Case selection?
Imaging for MVO, older devices; delay

15. Subset analysis
IMS III– CTA group
– with ICA and
MCA - positive

16. IMS -III

17. 31.5 36.6
46.9
0
20
40
60
MS PS RS
MRS<=2
MS
PS
RS
MERCI
PENUMBRA
SOLITAIRE
AJNR, Jan, 2013

18.  Randomised (Intervention Vs Standard medical
therapy)
 Documented site of occlusion.
 Time based: 6 hrs (initiation of IA therapy)
 Small Core
 Predominantly stent retrievers.

19. Criterion:
1. NIHSS ≥ 2
2. Distal ICA; MCA (M1 or M2); ACA (A1 or A2)
3. Initiate IA < 6 hours
MR CLEAN
(Netherlands)
Recruited: 502
patients

20. Criterion
1. NIHSS > 5
2. Distal ICA; MCA (M1 or M1 equivalent)
3. NCCT - ASPECTS of 6 to 10.
4. CTA collateral > 50% of territory
5. Randomize and initiate IA < 12 hours
1. NCCT to groin puncture ≤ 60 minutes
2. NCCT to first reperfusion ≤ 90 minutes
ESCAPE
(CANADIAN)
Recruited: 316 patients
Stopped early !!
Met prespecified
O’Brien-Fleming
stopping boundary.

21. Criterion:
1. Distal ICA; MCA (M1 or M2)
2. CT oar MR perfusion
1. Mismatch ratio 1.2
2. Core < 70 ml
3. Present within IV tPA time window;
Groin puncture < 6 hours
EXTEND IA
(AUSTRALIAN)
Recruited: 70 patients
Stopped
early !!
Prespecified
Stopping
criterion met

22. Criterion:
1. NIHSS 8- 29
2. Distal ICA; MCA (M1)
3. CT or MR perfusion
1. Mismatch ratio 1.8
2. Core < 50 ml {Later relaxed}
3. ASPECTS > 6
4. Present within IV tPA time window; Groin
puncture < 6 hours
SWIFT PRIME
(USA)
Recruited: 196 patients
Stopped early !!
Prespecified Stopping
criterion met

23. Criterion:
1. NIHSS ≥ 6
2. Distal ICA; MCA (M1)
3. CT ASPECTS ≥ 6
4. Groin puncture < 8 hours
REVASCAT
(SPANISH)
Recruited: 206 patients

24. Comparison of protocol- Randomised (Intervention
Vs Standard medical therapy)
• Documented MVO.- ICA, MCA (M1, M2)
• Time based: 6 hrs (initiation of IA therapy)-
(8 hrs – REVASCAT; 12 hrs – ESCAPE)
• Small Core - CT ASPECTS ≥ 6
• CTP – EXTEND IA; SWIFT PRIME
• Predominantly stent retrievers.
• 86.1 to 100% (100 % in EXTEND IA & SWIFT
PRIME)

25. TICI 2B/3 – 59% - 88% - (previous trials 25%, 41%)
Recanalization – TICI 2B/3

26. Absolute Benefit (good outcome) : 13.5% to 31.4%
(Statistically significant)
mRS (90 d)

27. no significant difference
sICH

28. Device complication

29. Absolute mortality benefit : 8.6%
(Statistically significant in ESCAPE)
Mortality

31. Comparison of NNT:
EVT: NNT (benefit) - 3.1 to 4.2 (excluding MR CLEAN)
IV tPA ( 3 – 4.5 hours) – 13.8 (ECASS – 3)
Primary PCI (prevent re-infarction) – 33

32. IV tPA – Does it make a difference?
Subgroup analysis (ESCAPE) -
Received intravenous r-tPA – 235; (OR, 2.5 [1.6–4.0])
No intravenous r-tPA – 76; (OR, 2.6 [1.1– 5.9])
Conclusion:
Stent retriever based mechanical thrombectomy to be
offered if there are contraindications to IV tPA

33. Advanced Imaging:
CTA used to detect MVO
CT Perfusion:
 SWIFT Prime – Criterion changed (71 with perfusion; 125 without)
 possibility that patients who may have responded to therapy
were excluded.
Site of occlusion should be documented:
 studies not designed to validate the utility of the advanced
imaging selection criteria

34. Techniques:
 Stent retriever
 Stent retriever + Proximal balloon guiding
catheter (flow arrest)
 Stent Retriever +
Lesional aspiration
(Distal access catheters)Humphries W, Hoit D, Doss VT, et al. Distal aspiration with retrievable stent assisted thrombectomy for the treatment of acute
ischemic stroke. J Neurointerv Surg. 2015;7:90-94.
Nguyen TN, Malisch T, Castonguay AC, et al. Balloon guide catheter improves revascularization and clinical outcomes with the
Solitaire device: analysis of the North American Solitaire Acute Stroke Registry. Stroke. 2014;45:141-145.

35. Proximal Carotid Occlusion/ Stenosis:
 ESCAPE (adjusted OR, 9.6; 95% CI, 2.6–35.5) ;
 MR CLEAN (adjusted OR, 1.43; 95% CI, 0.78–
2.64)
 Not clear on the best management strategy for the
proximal lesion
 When and how to treat
 Angioplasty Vs stenting

36. AHA/ ASA guideline 2015:
Patients should receive endovascular therapy with a stent
retriever if they meet all the following criteria (Class I; Level of
Evidence A). (New recommendation):
 prestroke mRS score 0 to 1
 acute ischemic stroke receiving intravenous r-tPA within 4.5
hours of onset
 causative occlusion of the internal carotid artery or proximal
MCA (M1)
 age ≥18 years
 NIHSS score of ≥6
 ASPECTS of ≥ 6
 treatment can be initiated (groin puncture) within 6 hours of
symptom onset

37. AHA/ ASA guideline:
 Carefully selected patients with anterior circulation
occlusion who have contraindications to intravenous r-
tPA, endovascular therapy with stent retrievers
completed within 6 hours of stroke onset is reasonable
(Class IIa; Level of Evidence C).
 Carefully selected patients with acute ischemic stroke in
whom treatment can be initiated (groin puncture) within 6
hours of symptom onset and who have causative
occlusion of the M2 or M3 portion of the MCAs, anterior
cerebral arteries, vertebral arteries, basilar artery, or
posterior cerebral arteries (Class IIb; Level of Evidence
C)

38. AHA/ ASA guideline:
 Stent retrieval may be reasonable for patients
with acute ischinitiated (groin puncture) within 6
hours emic stroke in whom treatment can be of
symptom onset and who have prestroke mRS
score of >1, ASPECTS >1, ASPECTS <6, or
NIHSS score <6 and causative occlusion of the
internal carotid artery or proximal MCA (M1)
 Observing patients after intravenous r-tPA to
assess for clinical response before pursuing
endovascular therapy is not required to achieve
beneficial outcomes and is not recommended.
(Class III; Level of Evidence B-R).

39. STRUCTURE of STROKE care systems:
Should be transported rapidly to the closest available
certified primary strokecenter or comprehensive stroke
center
Regional systems of stroke care: Initial emergency
care (IV tPA)→ Centers capable of performing
endovascular stroke treatment.
Experienced stroke center with rapid access to
cerebral angiography and qualified neuro-
interventionalists.

40. Comparison of IAT processes.
Brijesh P. Mehta et al. J Am Heart Assoc 2014;3:e000963
© 2014 Brijesh P. Mehta et al.
Time is the key ….post Quality improvement (QI) –
Parallel processing
Pre and post Quality improvement (QI) – Parallel processing

41. •68/M, DM, HTN, CAD, underwent PTCA to
LAD
•Admitted for surgery of aortic stenosis.
•Double anti-platelets was stopped
•Patient developed acute onset right side
weakness with aphasia.
IV- tPA given, no improvement

43.  Left hemiplegia, left UL and LL 0/5
 5:14AM

44. 6:22AM

45. 8:07 AM
Patient made gradual recovery
Left LL 4/5 and UL 3/5 - 30 day follow up
mRS at 90 days- 0

46. • 60 years old female.Acute onset left hemiparesis and left
facial weakness; CT Brain , CTP and CTA done 6 1/2 hours after
ictus.

47. Issues …
Beyond 6 hours – Should you consider MT?
ESCAPE: up to 12-hours – positive trial
6 hours
49 patients
rate ratio, 1.7; (95% CI, 0.7 to 4.0)
Not significant; however few numbers.
REVASCAT: upto 12 hours, positive trial
Data not provided.

48.  Category: < 6H Vs > 6 h (or) unknown time [UOS] (or)
wake up [WUS].
 T < 6H – 654
 T > 6H - 205 (128 T > 6H, 55 WUS and 22 UOS).
Non significant difference in clinical
outcome, recanalization rates and SICH

49. Tissue at risk/ core > 3
Later time windows/
wake up

50.  63 /M, AVR, Coumadin
 INR of 2.5
 RT hemiparesis - 2/5 in leg
and 0/5 in arm
 Global aphasia
CBF CBV
Solitaire
stent was
deployed
Issues….. Intracranial atherosclerosis

51. TREVO, Stryker Neurovascular
REVIVE, Codman
Neurovascular
ERIC, Microvention
Technique ……

52. Techniques..
• 6mm vs 4mm
•Length
•2 retriever
•ADAPT
•Proximal occlusion and
aspiration
•Distal aspiration
•GA vs LA ??

53.  Recent trials are watershed in stroke
management --- further evolution
 Mechanical recanalization is part of stroke
treatment
 Focus on building stroke intervention centers
and network of peripheral and referral stroke
centers
 Challenge and responsibility !

55. • 60 years old female.
• h/o hypertension and hypothyroidism
• Acute onset left hemiparesis and left facial weakness
• No history of LOC/seizures
• CT Brain , perfusion and angio done 6 1/2 hours after
ictus.

58. 2 months later

59. • 41 year old male, Severe MR, EF 20%
• Stroke in sleep, NIHSS 14 on admission

60. 6:22AM

61. Patient made gradual recovery
Left LL 4/5 and UL 3/5 - 30 day follow up
mRS at 90 days- 0

62. • Retrospective; September 2010 and April 2013
• Compared proximal vs distal approach
• Weight-adapted bolus of tirofiban followed by a continuous infusion
for 24 h to prevent in-stent thrombosis
• After exclusion of cerebral hemorrhage on follow-up imaging, 500 mg
of acetylsalicylacid (ASA) and 300 mg of clopidogrel

65. ISC 2013

66.  Left hemiplegia, left UL and LL 0/5
 5:14AM

67. 6:22AM

68. 8:07 AM
Patient made gradual recovery
Left LL 4/5 and UL 3/5 - 30 day follow up
mRS at 90 days- 0

69.  63 /M, AVR, Coumadin
 INR of 2.5
 RT hemiparesis - 2/5 in leg
and 0/5 in arm
 Global aphasia
CBF CBV
Solitaire stent was deployed

70. • 60 years old female.Acute onset left hemiparesis and left
facial weakness; CT Brain , CTP and CTA done 6 1/2 hours after
ictus.
Mca aneurysm coiling vs surgery

71. For more information on:
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Dr Vipul Gupta