To clarify safety and efficacy outcomes in patients not meeting DAWN and/or DEFUSE-3 criteria but receiving off-label EVT.
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:
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).
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).
- 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.
- 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.