Defining the Therapeutic Ceiling of Endovascular Thrombectomy in Large-Core Stroke: Beyond the Limits of ASPECTS

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BACKGROUND: Recent trials established the efficacy of thrombectomy for large-core stroke by utilizing the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) as a pragmatic tool. However, whether this topographical scoring captures the therapeutic ceiling, or the upper threshold of infarct volume where the benefit of reperfusion diminishes, remains unclear. METHODS: Leveraging a nationwide multicenter registry in Korea (2022-2024), we compared the prognostic value of quantitative volumetry and ASPECTS in thrombectomy-treated patients. We analyzed discordance between ASPECTS and volumetry derived from diffusion-weighted imaging, computed tomography perfusion, and noncontrast computed tomography. The primary outcome was poor functional outcome (90-day modified Rankin Scale score 5-6). To estimate treatment effects across specific volume spectra, we conducted target trial emulations that stratified causal estimates by volumetric thresholds, with the ordinal 90-day modified Rankin Scale score shift as the primary outcome. RESULTS: Among 552 patients, the mean age was 70.4±12.6 years, and 319 (57.8%) were men. Patients classified as large core by ASPECTS but not by diffusion-weighted imaging volumetry (ASPECTS-only large core) had poor outcome proportions comparable to the both small-core group (11.8% versus 11.7%), with no excess risk after adjustment. Conversely, volumetric confirmation of large core across diffusion-weighted imaging, computed tomography perfusion, and noncontrast computed tomography consistently predicted poor prognosis regardless of ASPECTS (adjusted odds ratio, 6.92 [95% CI, 2.58-19.34] for the diffusion-weighted imaging-only large-core group). In the target trial emulations, the overall benefit of thrombectomy was attenuated (common odds ratio, 0.56 [95% CI, 0.31-1.03]). Stratified analyses delineated a therapeutic ceiling, with benefit in the 50 to 110 mL range (common odds ratio, 0.38 [95% CI, 0.15-0.97]) disappearing in extensive infarctions >110 mL. CONCLUSIONS: Quantitative volumetry provided better prognostic discrimination and identified ≥110 mL as a therapeutic ceiling where the benefit of thrombectomy becomes negligible. These findings advocate integrating volumetric thresholds into patient selection to minimize futile reperfusion and prioritize safety, serving as a critical refinement to current topographical scoring.

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