IVtPA vs Mechanical thrombolysis, after 3-hours of stroke (Presented at Neocon 2015 conference)

1. IVtPA vs Mechanical thrombolysis,
after 3-hours of stroke……
Vipul Gupta
Neurointerventional Surgery
(Interventional Neuroradiology)
Institute of Neurosciences
Medanta the Medicity

2. IV tPA- indications
; ASA/AHA guidelines
Stroke - 2013
Less than 10% patients are eligible

3. 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….

4. 3- 6 hours
PWI/ DWI > 1.2
Non significant
difference in
good outcome

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

7. Case selection- mechanical
thrombectomy
• 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)

9. Issues
• 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 !!!

11. 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

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

13. 31.5 36.6
46.9
0
20
40
60
MS PS RS
MRS<=2
MS
PS
RS
MERCI
PENUMBRA
SOLITAIRE
AJNR, Jan, 2013

14. 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

15. 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.

16. 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

17. 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

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

19. 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)
• (NIHSS scores were 17 (interquartile range, 13–21)

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

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

22. no significant difference
sICH

23. Device complication

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

26. 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

27. 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

28. 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)
Waiting after IV tPA not required (Class III)

29. 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.

30. • 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

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

32. 6 hrs aftre onset…

33. •
60 years old female.Acute onset left hemiparesis and left
facial weakness; CT Brain , CTP and CTA done 6 1/2 hours
after ictus.

34. MT beyond 3-Beyond hours…
hours
• IV tPA not beyond 4.5 hours …..
• Mechanical recanalization should be consider
as per guidelines
• Beyond 6-hours , careful selection may be
• Focus on building stroke intervention centres
and network of peripheral and referral stroke
centres
• Challenge and responsibility !

36. 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

37. AHA/ ASA guideline:
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).