1. Extended Window Thrombectomy
Setareh Omran, MD
Vascular Neurology Fellow

2. Study
mRS 0-2 at 90d (%)
mRS score reduction, 90d, OR (95% CI)
Death at 90d (%)
sICH (%)
TICI 2b/3 (%)-
MR CLEAN
19.1/32.6
1.67 ( )
22/21
6.4/7.7 (90d) 59
ESCAPE
29.3/53
3.1 ( )
19/10.4
2.7/3.6 (90d)
72.4
EXTEND-IA
40/71
2 ( )
20/9
6/0 (at 36 hrs) 86
REVASCAT
43.7/28.2
1.7 ( )
16/18
2/2 ( 90d) 66
SWIFT PRIME
35/60
1.7 ( )
12/9
3/0 (27 hrs) 88
HERMES
26.5/46
2.49 ( )
18.9/15.3
4.3/4.4 71

3. Who Do We Know Benefits? Clinical criteria
Age >18 (no clear upper age limit)
Functionally independent at baseline (mRS ≤2)
Significant neurologic deficit (NIHSS ≥6)
Onset to groin puncture ≤6hrs
Radiological criteria
No Intracranial hemorrhage
No large established stroke (<1/3 MCA territory)
Anterior circulation LVO (ICA and/or M1 MCA segments)

4. What about the late presenters?
Majority of AIS pts present beyond the traditional window
14-28% of AIS are unwitnessed or wake up strokes
DAWN and DEFUSE 3 attempted to answer these questions
Goal is to treat “Slow Progressors”

5. DAWN Trial Overview
Evaluate the effectiveness and safety of mechanical thrombectomy in AIS pts in an extended time window (6-24 hours from last known well)
Specifically targeted witnessed strokes out of the traditional time window, unwitnessed strokes, and wake-up strokes
Inclusion criteria based on mismatch between clinical severity of stroke symptoms and infarct core size -- Shifts the paradigm from “time is brain” to image driven evaluation of salvageable brain tissue

6. Multi-center, prospective, randomized trial
Multi-center, prospective, randomized trial. Patients randomized to endovascular thrombectomy + standard care or standard care alone.
Inclusion Criteria:
Clinical
Imaging
signs/symptoms of stroke
ICA, MCA M1 segment + few cases of M2
Failed IV-tPA or contraindication to IV-tPA
Mismatch based on MRI or CTP:
0-20cc core infarct + NIHSS ≥10 (and age ≥ 80 yo)
0-30cc core infarct + NIHSS ≥10 (and age < 80 yo)
31-50cc core infarct + NIHSS ≥20 (and age < 80 yo)
Age ≥18 yo
Baseline NIHSS ≥10 (measured within 1 hr of infarct core volume assessment)
Last known well 6-24 hours
mRS 0-1 at baseline
Anticipated life expectancy > 6 months

7. Outcomes
Primary End point: Score on utility-weighted mRS at 90 days (Scale 0-10), Functional independence at 90 days (mRS 0-2)
Results: Of 206 patients enrolled (107 treatment, 99 control), with median LKN to puncture 13.6hr
UW-mRS at 90d had 2.1 absolute difference (5.5 in thrombectomy, 3.4 in control group).
Functional independence at 90 days: 36% absolute difference (similar independence as in HERMES) with NNT 2.8.
TICI 2b/3 recanalization rate 84% (71% in HERES meta-analysis). No significant difference in safety outcomes

8. DEFUSE 3 Evaluate extended window thrombectomy. Inclusion Criteria:
Clinical
Imaging
Signs/symptoms of stroke
ICA, MCA M1 segment + one case of M2
Last Known Well 6-16 hours
Infarct size <70ml by CTP (RAPID) or MRI-DWI, ratio of volume of ischemic to infarct of 1.8 or more
Age ≥18 yo
Baseline NIHSS ≥6
mRS 0-2 at baseline
Anticipated life expectancy > 6 months

9. Outcomes Primary Outcome: mRS at 90 days
Results: total of 182 patients (92 to endovascular, 90 to medical therapy)
Endovascular therapy plus medical therapy, as compared with medical therapy alone, was associated with a favorable modified Rankin scale at 90 days of 0-2 (45% vs 17%, p<0.001) with NNT 3.5.
The 90-day mortality rate was 14% in the endovascular-therapy group and 26% in the medical-therapy group (P = 0.05), and there was no significant between-group difference in the frequency of symptomatic intracranial hemorrhage (7% and 4%, respectively; P = 0.75).

10. Endovascular Screening Criteria
For ALL patients with
NIHSS ≥6
LKN<24hrs
Assess the following:
Clinical
Age
Last seen well
Premorbid baseline mRS
Candidacy for IV tPA
Radiological
Hemorrhage excluded
Evidence of ischemic stroke
Presence of LVO (ICA, M1)
Core infarct volume
Quality of collateral
Need for advanced imaging
Using screening criteria to classify patients as:
Proven (6 hr time window)
Proven (under DAWN or DEFUSE criteria)
Unlikely
to benefit from endovascular therapy.

11. Proven Benefit Endovascular Criteria (≤6 hrs)
Treatment process for all cases initiated by Stroke and Endovascular Team
Clinical (must meet all)
NIHSS ≥6
Time ≤6 hours from LKW to expected groin puncture
Age ≥18 yo
Premorbid condition
-mRS ≤2
-Life expectancy >12 months
 Radiological (must meet all)
No intracranial hemorrhage
Intracranial ICA or MCA M1 occlusion (CTA or MRA)
Small core infarct volume by either imaging modality
CT criteria:
-ASPECTS ≥ 7 on Non con HCT, Core infarct <1/3 MCA territory on CTP
MRI criteria:
-Core infarct <1/3 MCA territory by DWI by ABC/2 measurement

12. Proven to Benefit Endovascular Criteria (6-24 hrs)
Treatment process for all cases initiated by Stroke and Endovascular Team
Clinical (must meet all)
NIHSS ≥10 by DAWN, NIHSS ≥6 by DEFUSE
Time: hours by DAWN, 6-16 hours by DEFUSE
Age: ≥18 yo
Premorbid condition
-mRS ≤1
-Life expectancy >6 months
Radiological (must meet all)
No intracranial hemorrhage
Intracranial ICA or MCA M1 occlusion (CTA or MRA)
Small core infarct volume by DWI-MRI or CTP based on DAWN or DEFUSE criteria

13. Unlikely to Benefit Endovascular Criteria
No endovascular treatment offered
Clinical (if meets any)
NIHSS <4
Time: >24 hr from LKW
Premorbid condition
-mRS ≥3
-Life expectancy of <12 months
Does not meet stratisfied DAWN clinical criteria (if 6-24 hrs from LKN)
or DEFUSE 3 clinical criteria (if 6-16 hrs from LKN)
Radiological (if meets any)
Intracranial hemorrhage
No proximal LVO
Distal arterial occlusion (Distal M2, M3, A1)
Large established core infarct by either imaging modality
CT criteria: ASPECTS ≤6 on Non con CT
CTP criteria: Infarct core >1/3 MCA territory (70-100cc)
MRI criteria: Infarct core >1/3 MCA territory ( cc)