Endovascular therapy (EVT) is recommended as the standard treatment for acute ischemic stroke (AIS) due to large-vessel occlusion (LVO) in the anterior circulation. Recent randomized controlled trials have shown that EVT yields better functional outcomes than medical management alone, even in patients with LVO-AIS and a large ischemic core. However, a substantial proportion of patients still have poor 90-day outcomes despite successful recanalization, prompting an important clinical question: which pre-existing brain vulnerabilities might limit the benefit of EVT in patients with LVO-AIS?
One potential vulnerability is white matter lesions (WMLs) —chronic changes visible on brain imaging that often reflect underlying cerebral small-vessel disease. Severe WMLs have been linked to worse outcomes after stroke and may indicate reduced brain resilience to acute injury and reperfusion-related complications. However, many prior observational studies lacked an appropriate control group, making it difficult to determine whether EVT confers meaningful benefit in patients with severe WMLs.
To address this gap, investigators performed a secondary analysis of the randomized ANGEL-ASPECT trial (ClinicalTrials.gov: NCT04551664), a multicenter study conducted at 46 comprehensive stroke centers in China. ANGEL-ASPECT enrolled patients with acute anterior-circulation LVO and a large ischemic core, who were assigned to receive either EVT plus medical management or medical management alone. In the present analysis, baseline WML severity was graded on pretreatment noncontrast CT (NCCT) using the van Swieten Scale, and 90-day functional outcomes were assessed using the modified Rankin Scale (mRS). The investigators compared outcomes between treatment groups within prespecified WML strata and formally tested whether WML severity modified the treatment effect of EVT. This study was published online in the Chinese Medical Journal on February 04, 2026.
The analysis found that among patients with absent-to-moderate WML burden , EVT was associated with a favorable shift toward better 90-day functional outcomes compared with medical management alone. In contrast, among patients with severe WMLs , the point estimates suggested a less pronounced benefit that did not reach statistical significance. Importantly, however, the treatment-by-WML interaction was not significant, providing no robust evidence that baseline WML severity modifies EVT’s treatment effect in this trial population. To strengthen the interpretation, the investigators conducted supplementary analyses using MRI-based WML assessment. When WML severity was rated on T2-FLAIR MRI using the Fazekas scale, results were consistent with the primary CT-based findings. In addition, CT- and MRI-based ratings showed substantial agreement in identifying severe WML burden, supporting the clinical feasibility of NCCT-based WML grading in acute treatment workflows.
Taken together, these findings suggest that EVT remains clearly beneficial in patients with anterior-circulation LVO and a large ischemic core when WML burden is absent-to-moderate . For patients with severe WMLs , the data indicate greater uncertainty: the estimated benefit appeared attenuated, but confidence intervals were wide and statistical significance was not achieved, likely reflecting the relatively small sample size of the severe-WML subgroup.
The authors caution that these findings should not be interpreted as definitive evidence against EVT in patients with severe WMLs. Rather, they highlight the need for adequately powered pooled analyses of randomized trials to determine whether WML burden should be incorporated into treatment-selection frameworks for LVO-AIS. If confirmed, WML assessment may support more individualized decision-making by identifying patients in whom the functional benefit of EVT is less certain and in whom procedural risks and pre-existing brain vulnerability warrant particularly careful consideration.
Reference
DOI: http://doi.org/10.1097/CM9.0000000000003993
About Yilong Wang, Zhongrong Miao, Zan Wang (Beijing Tiantan Hospital, Capital Medical University), and Chenhui Liu (The First Affiliated Hospital of Zhengzhou University)
Yilong Wang, MD, PhD, is a Professor and Chief Physician at Beijing Tiantan Hospital, Capital Medical University, and a doctoral supervisor. His research focuses on clinical studies of cerebral small vessel disease. He has led multiple national-level research projects supported by the Ministry of Science and Technology, the National Science Fund for Distinguished Young Scholars, and the Beijing Municipal Science and Technology Commission. As the corresponding author, he has published more than 100 high-impact papers in journals including The N ew England Journal of Medicine, JAMA , BMJ , The Lancet Neurol ogy , and Circulation , and holds 12 invention patents, including one international patent.
Zhongrong Miao , MD, PhD, is a Professor and Chief Physician at Beijing Tiantan Hospital, Capital Medical University, and a doctoral supervisor. He serves as Chief Scientist of Interventional Neuroradiology, Department of Neurology, Beijing Tiantan Hospital. His work addresses key unmet needs in the prevention and treatment of cerebrovascular diseases. He has played a leading role in conducting the ANGEL series of studies in China, with research published in journals such as The N ew England Journal of Medicine , The Lancet , and JAMA . He has contributed to multiple expert consensus statements and clinical guidelines for ischemic cerebrovascular diseases.
Zan Wang , MD, is a postdoctoral research fellow and attending physician in the Department of Neurology, Beijing Tiantan Hospital, Capital Medical University (postdoctoral supervisor: Professor Yilong Wang). His research focuses on clinical studies of cerebral small vessel disease and neuroimaging. He holds one invention patent and contributed to the expert consensus Neuroimaging Diagnostic Criteria and Standardized Terminology for Cerebral Small Vessel Disease in China .
Chenhui Liu is a PhD candidate in Neurology at the First Affiliated Hospital of Zhengzhou University (supervisor: Professor Yilong Wang). His research focuses on clinical studies of cerebrovascular disease and neuroimaging. He has participated in large-scale clinical studies, including INSPIRES and EMPHASIS, and has contributed to projects supported by major national science and technology programs.
Chinese Medical Journal
Data/statistical analysis
Not applicable
White matter lesions modifying endovascular therapy outcomes in large ischemic core stroke: A secondary analysis of the ANGEL-ASPECT trial
4-Feb-2026
None.