Large core RCT session

Endovascular therapy for large-core anterior circulation ischemic stroke: current evidence and future

Despite six randomized controlled trials (RCTs) demonstrating the benefits of endovascular treatments for large-core anterior circulation ischemic stroke without significantly increasing the risk of symptomatic intracranial hemorrhage, and also with long-term follow-up showing that the benefits of thrombectomy on neurological outcomes become more evident at 1 year compared to 90 days, clinical practice correspondingly has been modified steadily behind time. Updates in guidelines may be the most significant driving force.

The Chinese stroke association guidelines on reperfusion therapy for acute ischaemic stroke 2024 recommend the following: mechanical thrombectomy is recommended for patients with acute ischaemic stroke who present with National Institute of Health Stroke Scale ≥6 and Alberta Stroke Programme Early Computed Tomographic Score ≥3, with occlusions in the internal carotid artery or M1 within 24 hours of last known normal (Class I, Level A). The 2024 SNIS guidelines recommend similarly that in patients with anterior circulation ELVO who present within 24 hours of last known normal with large infarct core (70-149 mL or ASPECTS 3-5) and meet other criteria of RESCUE-Japan LIMIT, SELECT2, ANGEL-ASPECT, TESLA, TENSION, or LASTE trials, thrombectomy is indicated (Class I, Level A). Although the European guideline has not yet been updated, the number of thrombectomies performed in low ASPECTS patients has significantly increased.

Mechanical thrombectomy for patients with ASPECTS 0–2 has not been widely adopted. A  meta-analysis including four RCTs (ANGEL-ASPECT, SELECT2, TENSION, and LASTE) with a total of 301 patients showed that the proportion of 90-day functional independence (modified Rankin Scale [mRS] score 0–2) was significantly higher in the thrombectomy group than in the medical treatment group (OR 1.62 [1.29; 2.04], p < 0.001). A sensitivity analysis including three of those trials, which primarily used CT for selection, yielded consistent results (OR 1.47 [1.05; 2.05], p = 0.02). In the ANGEL-ASPECT study, the infarct volume in the ASPECTS 0–2 subgroup was limited to 70–100 mL. The LASTE trial, which contributed 60.1% of the data, included 181 patients aged 18–80 years with ASPECTS 0–2. Approximately 86% were recruited with MRI, with a baseline infarct volume of about 155 mL. More than 30% of these patients received intravenous thrombolysis. Consistent with the whole study group, the thrombectomy group had significantly higher proportions of 90-day and 180-day functional independence (mRS score 0–2). The proportion of intracranial hemorrhage within 24 hours in the thrombectomy group was 75.3% versus 59.1% in the medical treatment group. Approximately 13% of patients underwent decompressive craniectomy within 7 days, comparable between the two groups. However, in ANGEL-ASPECT trial the proportion of decompressive craniectomy was higher in the thrombectomy group among patients who did not achieve successful reperfusion. In the era of  thrombectomy for large ischemic stroke, we may need to re-evaluate the timing of decompressive craniectomy and its impact on functional outcomes and mortality.

Regarding imaging assessment methods, ASPECTS based on diffusion-weighted imaging (DWI) may be lower than that based on non-contrast computed tomography (NCCT), especially in the hyperacute phase. Whether thrombectomy benefits are limited to patients with perfusion mismatch (mismatch ratio ≥1.2 or ≥1.8) is inconsistent between ANGEL-ASPECT and SELECT2. The LASTE study, based on MRI, showed that although patients without mismatch had overall larger infarct volumes and poorer prognosis, the therapeutic effect of thrombectomy on functional independence remained, with no differences in safety outcomes such as intracranial hemorrhage.

These findings challenge the role of ASPECTS as a patient eligibility for thrombectomy, prompting us to re-evaluate imaging markers such as “ischemic core” and “penumbra.” The ischemic core defined by NCCT, CT perfusion (CTP), or even pre-procedural DWI imaging may be reversible with timely reperfusion, with highly heterogeneous, micro-infarct cores, micro-penumbra and edema distributed in a mosaic pattern. The improved functional outcome in the thrombectomy group may not only be due to reduced infarct volume but also possibly related to decreased edema volume.

Although the six RCTs on large-core thrombectomy generally reached consistent conclusions, there are slight differences in patient criteria and imaging tools. Individual-level pooled analysis may further clarify target patients, to whom thrombectomy would be clearly benefit or detrimental, providing more practical paradigm for clinical practice.

Reference

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