Oedema reduction mediates thrombectomy benefit in large core stroke: secondary analysis of the TENSION trial

Purpose: Several recent trials have shown improved functional outcomes with endovascular thrombectomy (EVT) in patients presenting with large ischaemic lesions, yet the impact of reperfusion on lesion pathophysiology in this population remains incompletely understood. We hypothesised that EVT reduces ischaemic oedema formation and that attenuation of oedema mediates functional outcome improvement beyond changes in lesion extent. Methods: We performed a secondary analysis of the randomised TENSION trial, which enrolled patients with anterior circulation ischaemic stroke and baseline ASPECTS 3–5. Oedema progression was quantified as the change in CT-based net water uptake between baseline and follow-up non-contrast CT (ΔNWU), derived from relative hypoattenuation within the infarct. Lesion extent change was assessed by the difference in ASPECTS between baseline and follow-up imaging (ΔASPECTS). Associations of ΔNWU and ΔASPECTS with 90-day modified Rankin Scale (mRS) were tested using ordinal logistic regression. Mediation analyses estimated the proportion of EVT’s treatment effect on functional outcome explained by ΔNWU and ΔASPECTS. Results: Among 177 patients, median follow-up NWU was 28.5% (IQR: 19.2–36.6) and follow-up ASPECTS was 2 (IQR: 1–3). EVT was associated with substantially lower oedema progression (ΔNWU 4.7% vs 15.9% without EVT; P < .001). Mediation analysis suggested that a model-estimated 34% of EVT-related improvement in mRS was associated with reduced oedema formation (ΔNWU), whereas 14% was associated with lesion extent change (ΔASPECTS). In a sensitivity analysis using nonparametric bootstrap with 5000 resamples, the mediation signal remained robust for ΔNWU but was substantially weaker for ΔASPECTS. Conclusion: In large-core stroke, EVT was associated with significantly attenuated oedema progression between baseline and follow-up imaging. Reduced ischaemic water uptake was strongly associated with EVT benefit on 90-day functional outcome in mediation models, supporting oedema attenuation as a plausible mechanistic pathway of EVT benefit.