By Märit Jensen, MD
University Medical Center Hamburg-Eppendorf, Hamburg, Germany;
Clinical Stroke and Imaging Research (CSI) group
In recent years, the treatment of patients with acute stroke has improved dramatically, with endovascular thrombectomy (EVT) playing an important role. Whereas evidence of a treatment benefit of thrombectomy was originally limited to the first 6 hours of stroke onset, we have recently moved beyond this narrow time window.
The DAWN1 and DEFUSE 32 trials showed that thrombectomy in the late time window up to 24 hours and in unknown onset stroke is safe and highly effective in selected patients. Both trials used advanced imaging with either perfusion CT or MRI to enroll patients based on the concept of perfusion mismatch (DEFUSE 3) or clinical-core mismatch (DAWN). Independent from differences in the details of the imaging protocols, the common main idea of both trials was to include patients who present with large vessel occlusion but only a small infarct core, rendering them likely to benefit from reperfusion treatment regardless of time. This was strikingly confirmed by the treatment benefits in both trials that were larger than those of any previous trial of acute stroke treatment (+36% absolute increase of patients with independent outcome in DAWN and +28% in DEFUSE 3).
The other side of the coin is the fact that only a very small number of patients in the late and unknown time window meet these criteria. In a case series from a large stroke center, less than 3% of 2.667 stroke patients met either DAWN or DEFUSE 3-criteria3. Thus, we must face the challenge how to transfer the results of these trials to our daily clinical practice. Do we really need advanced imaging with perfusion CT or MRI to guide EVT in the late and unknown time window? And what to do if neither is available, or patients present with large vessel occlusion but do not meet the strict criteria of DAWN or DEFUSE 3?
The results of MR CLEAN LATE, which were presented end of October 2022 at the WSC in Singapore by Susanne Olthuis, provide answers to this question and will likely help to increase the number of patients in the late and unknown time window that may be benefit from thrombectomy. MR CLEAN LATE tested whether plain CT and CT-angiography is sufficient to identify patients for EVT in the late time window. The trial randomized patients with a proximal intracranial anterior circulation occlusion, with presence of poor, moderate, or good collateral flow as shown by CTA (only excluding those with no collaterals at all). Treatment with EVT had to be started between 6 and 24 h after symptom onset or last seen well. Key inclusion criteria further comprised a score of at least 2 on the NIHSS, while patients with ischemic lesions extending >1/3 of the territory of the middle cerebral artery were excluded. Patients were randomized to either EVT (n=255) or best medical treatment (n=247). The primary endpoint was an ordinal shift in the mRS at 90 days. As main result, there was a significant better outcome with thrombectomy than best medical treatment with an adjusted odds ratio of 1.68 (95% confidence intervals 1.21-2.33). An independent outcome (mRS 0-2) was more frequently achieved in the EVT group (39% vs. 34%), while mortality did not differ significantly between the groups (24% with EVT and 30% in the control arm). Symptomatic intracranial hemorrhage was more frequent in the EVT group (6.6%) than in control group (1.6%).
MR CLEAN LATE adds an important piece of information to the question of thrombectomy in the late and unknown time window. While DAWN and DEFUSE 3 were landmark trials providing strong proof of concept for the benefit of reperfusion treatment in patients with tissue at risk of infarction independent from time, MR CLEAN LATE represents an important step towards a broader application of EVT in the late and unknown time window. We may still have to wait for the full publication of the trial results before international guidelines may be updated. In the meantime, however, in situations where no advanced imaging is available, stroke physician around the world may feel encouraged to go ahead with thrombectomy in patients with large vessel occlusion in the absence of extended early infarct signs.
- Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med. 2018;378:11-21
- Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med. 2018;378:708-718
- Jadhav AP, Desai SM, Kenmuir CL, Rocha M, Starr MT, Molyneaux BJ, et al. Eligibility for endovascular trial enrollment in the 6- to 24-hour time window: Analysis of a single comprehensive stroke center. Stroke. 2018;49:1015-1017
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