Time-Dependent Impact of Mismatch Profiles on Outcomes Following Endovascular Thrombectomy for Large Ischemic Stroke

BACKGROUND: Endovascular therapy (EVT) has demonstrated efficacy in patients with large core infarctions, yet favorable outcomes remain limited. Although mismatch profiles have long informed EVT decision-making in small-core strokes, their prognostic significance in large-core infarcts remains uncertain and may be affected by time from symptom onset. This study aims to evaluate the relationship between mismatch profiles, time distribution, and EVT efficacy in patients with large ischemic cores. METHODS: This was a secondary posthoc analysis of the ANGEL-ASPECT trial (Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core) in patients with large ischemic cores randomized to EVT or medical management. The primary outcome was the modified Rankin Scale score of 0 to 3 at 90 days. Analyses were stratified by mismatch profile (mismatch ratio ≥1.8 and volume ≥15 mL) and onset-to-imaging time (≤6 hours versus >6 hours). RESULTS: For the primary end point (modified Rankin Scale score, 0–3 at 90 days), no significant treatment-by-time interaction was observed ( P for interaction=0.412); within time strata, treatment-by-mismatch interaction tests were also nonsignificant (≤6 hours, P for interaction=0.166; >6 hours, P for interaction=0.301). In the early window (≤6 hours), EVT was associated with higher odds of favorable functional outcome (modified Rankin Scale score, 0–3 at 90 days) in patients with mismatch (48.9% versus 28.4%; odds ratio, 2.41 [95% CI, 1.28–4.55]; P =0.006), but not in those without mismatch (23.8% versus 27.3%; odds ratio, 0.83 [95% CI, 0.21–3.29]; P =0.795). In the late window (>6 hours), EVT was not associated with a significant improvement in modified Rankin Scale score 0 to 3 in either subgroup. CONCLUSIONS: Among patients with large infarct cores, the absence of mismatch was more common in the early time window and was associated with diminished benefit from EVT. These results suggest that mismatch evaluation—even in early presenting patients—may help inform treatment selection for patients with large ischemic cores. All interaction tests were nonsignificant; these findings are hypothesis‑generating and require prospective, prespecified confirmation. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04551664.