Extended Window Thrombectomy Setareh Omran, MD Vascular Neurology Fellow

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 (1.21-2.30) 22/21 6.4/7.7 (90d) 59 ESCAPE 29.3/53 3.1 (2.0-4.7) 19/10.4 2.7/3.6 (90d) 72.4 EXTEND-IA 40/71 2 (1.2-3.8) 20/9 6/0 (at 36 hrs) 86 REVASCAT 43.7/28.2 1.7 (1.05-2.8) 16/18 2/2 ( 90d) 66 SWIFT PRIME 35/60 1.7 (1.23-2.33) 12/9 3/0 (27 hrs) 88 HERMES 26.5/46 2.49 (1.76-3.53) 18.9/15.3 4.3/4.4 71

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)

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”

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

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

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

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

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).

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.

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

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: 6-24 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

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 (70-100 cc)