ivtpa vs mechanical thrombolysis, after 3-hours of stroke

IVtPA vs Mechanical thrombolysis, after 3-hours of stroke……

Vipul GuptaNeurointerventional Surgery

(Interventional Neuroradiology)Institute of Neurosciences

Medanta the Medicity

IV tPA- indications; ASA/AHA guidelinesStroke - 2013

Less than 10% patients are eligible

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….

3- 6 hoursPWI/ DWI > 1.2

Non significant difference in good outcome

•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

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

31.5 36.646.9

0

20

40

60

MS PS RS

MRS<=2

MSPSRS

MERCI

PENUMBRA

SOLITAIRE

AJNR, Jan, 2013

Criterion:

1.NIHSS ≥ 22.Distal ICA; MCA (M1 or M2); ACA (A1 or A2)3.Initiate IA < 6 hours

MR CLEAN(Netherlands)

Recruited: 502 patients

Criterion1.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 hours1. 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.

Criterion:

1.Distal ICA; MCA (M1 or M2)2.CT oar MR perfusion

1. Mismatch ratio 1.22. 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

Criterion:

1.NIHSS 8- 29

2.Distal ICA; MCA (M1)3.CT or MR perfusion

1. Mismatch ratio 1.82. 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

Criterion:

1.NIHSS ≥ 6

2.Distal ICA; MCA (M1)3.CT ASPECTS ≥ 6

4.Groin puncture < 8 hours

REVASCAT(SPANISH)

Recruited: 206 patients

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

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)

Waiting after IV tPA not required (Class III)

Beyond 6 hours – Should you consider MT?

ESCAPE: up to 12-hours – positive trial

6 hours49 patientsrate 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

6 hrs aftre onset…

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

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 !

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

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).