Recent evidence for mechanical thrombolysis

Recent evidence for mechanical thrombolysis

Vipul GuptaNeurointerventional Surgery

(Interventional Neuroradiology)Institute of Neurosciences

Medanta the Medicity

Acute stroke :Penumbra and Treatment Options

0

10

20

30

min

CB

F (m

l/1

00

g/m

in)

300 9060 4120 5 6 24 48h

Infarct-threshold

Penumbra

Vital tissue

InfarctSingle cellnecrosis

3

IV tPA- indications; ASA/AHA guidelinesStroke - 2013

Less than 10% patients are eligible

ECASS 352.4% vs. 45.2%; OR, 1.34; 95% CI,1.02 to 1.76; P=0.04.

IV tPA beyond 3-hours….

3- 6 hours

PWI/ DWI > 1.2

Non significant

difference in

good outcome

• 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

•Distal MCA – 44%

•Proximal MCA - 30%

•Terminal ICA - 6%

•Tandem cervical ICA/MCA

-27%

•Basilar artery- 30%

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)

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 !!!

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

Subset analysis

IMS III– CTA group

– with ICA and

MCA - positive

IMS -III

31.5 36.646.9

0

20

40

60

MS PS RS

MRS<=2

MS

PS

RS

MERCI

PENUMBRA

SOLITAIRE

AJNR, Jan, 2013

Randomised trials – General criterion

• Randomised (Intervention Vs Standard

medical therapy)

• Documented site of occlusion.

• Time based: 6 hrs (initiation of IA therapy)

• Small Core

• Predominantly stent retrievers.

MR CLEAN

(Netherlands)

ESCAPE

(CANADIAN)

EXTEND IA

(AUSTRALIAN)

SWIFT PRIME

(USA)

REVASCAT

(SPANISH)

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)

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

Recanalization – TICI 2B/3

Absolute Benefit (good outcome) : 13.5% to 31.4%(Statistically significant)

mRS (90 d)

no significant difference

sICH

Device complication

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

Mortality

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

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

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

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.

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

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)

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).

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 processingPre and post Quality improvement (QI) – Parallel processing

•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

• Left hemiplegia, left UL and LL 0/5

• 5:14AM

6:22AM

8:07 AM

Patient made gradual recovery

Left LL 4/5 and UL 3/5 - 30 day follow up

mRS at 90 days- 0

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

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.

• 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

Tissue at risk/ core > 3Later time windows/

wake up

• 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

Mechanical thrombolysis –TOC for MVOhours

• Recent trials are watershed in stroke management

• Mechanical recanalization is standard part of stroke treatment

• Issues – beyond 6 (7.3), tandem lesions, technique evolution, advacned imaging role…

• Challenge and responsibility !

• Focus on building stroke intervention centers and network of peripheral and referral stroke centers

• 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.

2 months later

• 41 year old male, Severe MR, EF 20%

• Stroke in sleep, NIHSS 14 on admission

6:22AM

Patient made gradual recovery

Left LL 4/5 and UL 3/5 - 30 day follow up

mRS at 90 days- 0

• 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

ISC 2013

Clinical …• Left hemiplegia, left UL and LL 0/5

• 5:14AM

6:22AM

8:07 AM

Patient made gradual recovery

Left LL 4/5 and UL 3/5 - 30 day follow up

mRS at 90 days- 0

• 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

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

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Dr Vipul Gupta

Thank you ….