This secondary analysis of the multicenter, randomized ANGEL-ASPECT trial investigated whether white matter lesion (WML) severity modifies the benefit of endovascular therapy (EVT) in patients with acute ischemic stroke due to anterior-circulation large-vessel occlusion and a large ischemic core. The trial enrolled 456 patients across 46 stroke centers in China between October 2020 and May 2022. WML severity was graded on pretreatment noncontrast CT using the van Swieten Scale; supplementary analyses used T2-FLAIR MRI and the Fazekas scale. The primary outcome was the distribution of 90-day modified Rankin Scale (mRS) scores. In patients with absent-to-moderate WMLs, EVT was associated with a favorable shift in mRS scores compared to medical management alone (adjusted common odds ratio [cOR] 2.15, 95% confidence interval [CI] 1.48-3.13, P<0.001). This benefit was less pronounced in patients with severe WMLs (adjusted cOR 2.25, 95% CI 0.95-5.30, P=0.065). No significant interaction between WML severity and treatment effect was detected (Pinteraction=0.888). For patients with absent-to-moderate WMLs, EVT also significantly increased rates of mRS scores 0-2 (adjusted OR 4.86, 95% CI 2.66-8.86, P<0.001), mRS scores 0-3 (adjusted OR 2.23, 95% CI 1.39-3.57, P=0.001), and early neurological improvement (adjusted OR 5.22, 95% CI 1.31-20.79, P=0.019). Supplementary MRI-based analyses yielded consistent results. The authors note that estimates within subgroups were underpowered and that future pooled analyses are needed to clarify the impact of WML severity on EVT outcomes.
When someone has a major stroke caused by a large blocked artery, doctors often perform a procedure called endovascular therapy to remove the clot. But a new analysis asks: does the health of the brain's white matter—the wiring that connects different brain regions—affect how well someone recovers from this treatment?
The study looked back at data from a large trial of 456 patients in China who had a major stroke. Researchers graded the severity of pre-existing white matter lesions (areas of small vessel damage often seen on brain scans) before treatment. They then compared how patients who received the clot-removal procedure fared against those who received only medical management.
The results showed a clear pattern. For patients with absent-to-moderate white matter damage, the clot-removal procedure was strongly linked to better functional recovery 90 days later. It shifted their outcomes toward greater independence. However, for patients with severe white matter damage, this benefit was less pronounced and did not reach statistical significance in this analysis. The study notes that the number of patients with severe damage was small, so these findings need confirmation in larger studies. The core message is that a patient's underlying brain health appears to be an important factor in their potential for recovery after a major stroke procedure.
What this means for you: The benefit of a stroke clot-removal procedure may be less pronounced for patients with severe pre-existing brain tissue damage.
View Original Abstract ↓
BACKGROUND: Severe white matter lesions (WMLs) have been linked to poorer functional outcomes following endovascular therapy (EVT) in patients with acute ischemic stroke (AIS) due to large-vessel occlusion (LVO). However, the absence of a control group in previous studies has limited the ability to determine the benefit of EVT to patients with severe WMLs.
METHODS: This work is a secondary analysis of the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core (ANGEL-ASPECT) trial, a multicenter, randomized controlled trial conducted at 46 comprehensive stroke centers across China, which enrolled 456 patients with AIS with anterior-circulation LVO and large ischemic cores between October 2020 and May 2022. WML severity was graded using the van Swieten Scale on pretreatment noncontrast computed tomography (CT). For supplementary analyses, WML severity was further assessed using T2 fluid-attenuated inversion recovery (T2-FLAIR) magnetic resonance imaging (MRI) and graded according to the Fazekas scale, with WMLs categorized into periventricular and deep subtypes. Treatment effect on the primary outcome (90-day modified Rankin Scale [mRS] score) was assessed using multivariable ordinal logistic regression, and a treatment-by-WML interaction term was tested to evaluate effect modification.
RESULTS: In patients with absent-to-moderate WMLs, EVT was associated with a favorable shift in the distribution of 90-day mRS scores (adjusted common odds ratio [cOR] 2.15, 95% confidence interval [CI, 1.48-3.13], P <0.001). However, this benefit was less pronounced in those with severe WMLs (adjusted cOR 2.25, 95% CI [0.95-5.30], P = 0.065). No significant interaction between WML severity and treatment effect was detected ( Pinteraction = 0.888). Similarly, only among patients with absent-to-moderate WMLs, EVT significantly increased rates of mRS scores of 0-2 (adjusted OR 4.86, 95% CI [2.66-8.86], P <0.001), the rates of mRS scores of 0-3 (adjusted OR 2.23, 95% CI [1.39-3.57], P = 0.001), and the rates of early neurological improvement (adjusted OR 5.22, 95% CI [1.31-20.79], P = 0.019) compared to medical management alone. Supplementary analyses using T2-FLAIR MRI to stratify patients by WML burden yielded results consistent with those of the primary analyses.
CONCLUSIONS: EVT significantly improved functional outcomes in patients with LVO-AIS with absent-to-moderate WMLs, while the benefit in those with severe WMLs appeared less pronounced. However, estimates within subgroups were underpowered. Future pooled analyses of randomized clinical trials with adequate statistical power are needed to clarify the impact of WML severity on EVT outcomes and to refine patient selection criteria.
REGISTRATION: ClinicalTrials.gov , No. NCT04551664.