EVT selection 6-24 hours after stroke: no thanks!

Key point:

    • 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:

Should we select all patients that could underwent stroke treatment or should we select only patients that would have a very high benefit from endovascular thrombectomy?

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:

Exclusion criteria

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).

Outcomes

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 patientsJ Neurointerv Surg. 2018 Nov;10(11):1033-1037. doi: 10.1136/neurintsurg-2018-013915. Epub 2018 May 17.

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