Select wisely: the ethical challenge of defining large core with perfusion in the early time window.

The pivotal stroke trials published in 2015 provided indisputable evidence of the benefit of thrombectomy in early window (0–6 hours) patients with anterior circulation emergent large vessel occlusion (ELVO) and small infarcts on non-contrast CT (NCCT), measured by ASPECTS 6–10.1–5 Since then, endovascular treatment of this population has been standard guideline-based care.6 Efforts, similar to the late window trials,7 8 are now directed at further expanding thrombectomy indications. Five trials are underway investigating the role of thrombectomy in patients with ELVO with ASPECTS <6, the 'large core' population for whom formal level I evidence is lacking (TENSION (NCT03094715); IN EXTREMIS-LASTE (NCT03811769); TESLA (NCT03805308); SELECT 2 (NCT03876457); and RESCUE-Japan LIMIT (NCT03702413)). Of these studies, all define large core using ASPECTS alone, except for one (SELECT 2). This study defines large core using ASPECTS or CT perfusion (CTP), and in doing so includes patients with poor NCCT ASPECTS (score <6) and also those with NCCT ASPECTS 6–10 with CTP-estimated ischemic core volumes ≥50 mL. Because the pivotal trials show unequivocally that patients with ASPECTS 6–10 and ELVO benefit from endovascular treatment in the 0–6-hour time window, we believe that this subgroup in SELECT 2 withholds proven class I treatment from eligible patients, raising concern for patient harm. As its name implies, CTP provides a measure of cerebral perfusion or, in the case of stroke, the strength of the collateral circulation.9 Even if one accepts the proposition that CTP can provide an accurate measure of cerebral blood flow (CBF),10 basic physiologic experiments and clinical studies have demonstrated that the progression from reversible ischemia to infarction is dependent on both CBF and the duration of ischemia.11–13 Taken together, the idea that one can accurately identify the region of irreversible injury (the core) from a threshold applied to a single snapshot …