
Key point:
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To clarify safety and efficacy outcomes in patients not meeting DAWN and/or DEFUSE-3 criteria but receiving off-label EVT.
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In this post, we have seen that DAWN (and DEFUSE-3) trials results opened a great debate and left us with a big question:
We concluded that the development of strict selection criteria could reduce the "therapy effect" of the treatment, despite it could increase the rate of patients with a good outcome.
Meanwhile after the publication of DAWN and DEFUSE-3 trials, American Heart Association 2018 guidelines offer:
- level 1A evidence for thrombectomy in the 6–16 hour time window for patients meeting DAWN and/or DEFUSE-3 trial criteria;
- level 2A evidence for patients in the 16–24 hour window meeting DAWN criteria.
Author's idea is that adherence to selective trial-defined criteria in late time windows may deny EVT to a population of patients who may benefit and prevent severe disability. In this study, Desai et al. identified patients presenting 6–24 hours after last known well (LKW) with a NIH Stroke Scale (NIHSS) score ≥6, and selected three groups: DAWN eligible, DEFUSE-3 eligible and non-DAWN non-DEFUSE-3 (NDND). Moreover patients in the NDND group were categorized as NDND ET group and NDND non-ET group.
Exclusion criteria for EVT were:
DAWN/DEFUSE-3 | Off-label EVT |
Infarct core volume >70mL | Infarct core volume >70mL |
Baseline mRS >2 | Baseline mRS >2 |
Absence of clinical core mismatch (DAWN) or target mismatch (DEFUSE-3)* |
Completed infarct° |
Distal occlusion (MCA-M2) |
*DAWN: age ≥80 years, NIHSS ≥10 and infarct volume ≤21mL; age <80 years, NIHSS ≥10 and infarct volume ≤31mL or NIHSS ≥20 and infarct volume ≤51mL. DEFUSE-3: ischemic core volume <70mL, mismatch ratio ≥1.8 and mismatch volume ≥15mL. ‡8% of patients had more than one reason for not receiving ET.
°no salvageable penumbra on perfusion imaging.
Primary end points were:
- symptomatic intracranial hemorrhage (sICH), defined as the presence of parenchymal hematoma type 2 on brain CT and/or MRI;
- neurological deterioration defined as an increase in NIHSS score of ≥4 points within 36 hours from treatment.
Secondary end points was stroke-related mortality.
The efficacy end point was 90-day functional independence (mRS score 0–2) and the technical efficacy end point for patients who underwent EVT was the rate of successful reperfusion (TICI score ≥2b).
NDND EVT group (n=37) | NDND non-EVT group (n=105) | Dawn EVT group (n=26) | DEFUSE-3 EVT group (n=24) | |
%TICI≥2b | 89% (33) | NA | 92% (24) | 88% (21) |
%early neurological recovery | 24% (9) | 11% (12) | 58% (15) | 46% (11) |
mRS 0-2 at 90 days | 30% (11) | 12% (13) | 54% (14) | 38% (9) |
%sICH | 8% (3) | 5% (5) | 4% (1) | 4% (1) |
Mortality | 24% (9) | 31% (33) | 15% (4) | 13% (3) |
Despite DAWN and DEFUSE-3 trials have different selection criteria, both reported a strong treatment effect (36% in DAWN and 28% in DEFUSE-3); the problem is that they have mutually exclusive populations of patients. In fact, 33% of DAWN eligible patients do not meet DEFUSE-3 criteria and 40% of DEFUSE-3 patients do not meet DAWN criteria.
Moreover, Authors reported that about 5% of all ischemic strokes in the 6–24 hour window that do not meet DAWN and/or DEFUSE-3 criteria, benefit from EVT.
Treatment effect rate reported in these article for patients with baseline mRs<2 is 24%; it is similar to DAWN and DEFUSE-3 rate (36% and 28% respectively).
In conclusion:
- ET may be safely offered to trial ineligible patients with less than trial-defined salvageable penumbra and/or MCA-M2 occlusions, particularly in patients with ischemic core volume of <70mL, baseline mRS 0–2, and age ≤80 years.
- Further liberalization of indications for EVT in late time windows is achievable.
Reference
- Shashvat M Desai, Marcelo Rocha, Bradley J Molyneaux, Matthew Starr, Cynthia L Kenmuir, Bradley A Gross, Brian Thomas Jankowitz, Tudor G Jovin, Ashutosh P Jadhav. Thrombectomy 6-24 hours after stroke in trial ineligible patients. J Neurointerv Surg. 2018 Nov;10(11):1033-1037. doi: 10.1136/neurintsurg-2018-013915. Epub 2018 May 17.