Background Malignant profiles were identified by imaging profiles and unfavorable outcomes that have poor response to reperfusion therapy. Many trials have used this profile in their inclusion criteria including large‐vessel occlusion acute ischemic stroke trials. We aimed to redefine the cutoff values for malignant profile in acute ischemic stroke patients with large‐vessel occlusion regardless of reperfusion therapy. Methods and Results Consecutive acute ischemic stroke patients with anterior large‐vessel occlusion were prospectively extracted from the National Cerebral and Cardiovascular Center Stroke Registry between March 2014 and December 2017. Diffusion‐Weighted Imaging‐Alberta Stroke Program Early Computed Tomography Score (DWI‐ASPECTS) and diffusion‐weighted imaging lesion ischemic core volume (Vol DWI ) were measured in acute ischemic stroke patients with large‐vessel occlusion with or without treatment. Unfavorable outcome was defined as a modified Rankin Scale score 5 to 6 at 3 months, and optimal DWI ‐ ASPECTS and Vol DWI for unfavorable outcome were assessed. In total, 198 patients (111 men, 77±13 years old) were enrolled. Median DWI ‐ ASPECTS was 7 (5‐9), and median Vol DWI was 55 (6‐134) mL . Among the patients, 72 (36%) patients underwent reperfusion therapy, and 83 (42%) had unfavorable outcomes. The threshold values for a malignant profile on receiver operating characteristic curve analysis for DWI ‐ ASPECTS and Vol DWI were 4 (area under the curve 0.78, P <0.01; sensitivity 0.71, specificity 0.75) and 71 mL (area under the curve 0.80, P <0.01; sensitivity 0.76, specificity 0.77), respectively. Conclusions The cutoff values for our redefined malignant profile were DWI ‐ ASPECTS 4 and Vol DWI 71 mL with no selection bias for reperfusion therapy in the real‐world clinical practice. Clinical Trial Registration URL : http://www.clinicaltrials.gov Unique identifier: NCT 02251665
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