Updated: Apr 15
Endovascular thrombectomy is a minimally invasive procedure that involves removing a blood clot from a blocked artery in the brain using a catheter and a device called a stent retriever. This procedure has been shown to be more effective in reducing disability than medical therapy alone in selected patients with ischemic stroke due to a large cerebral vessel occlusion. However, patients with large core infarct on noncontrast computed tomography (CT) or perfusion imaging have been underrepresented in thrombectomy trials, despite that such strokes account for approximately one fifth of large-vessel occlusion strokes. Consequently, the safety and efficacy of thrombectomy in patients with a larger ischemic burden have not been well established. These patients generally have poor neurologic outcomes, including progression of stroke symptoms, brain edema, and death.
Definition and Diagnosis of Large Ischemic Strokes
There is no universally accepted definition of large ischemic strokes, but several criteria have been used in previous studies to identify these patients. One of the most commonly used criteria is the Alberta Stroke Program Early CT Score (ASPECTS), which is a 10-point scale that assesses the extent of early ischemic changes in the middle cerebral artery (MCA) territory on noncontrast CT. ASPECTS is determined by dividing the MCA territory into 10 regions: caudate nucleus, lentiform nucleus, insula, internal capsule, anterior MCA cortex, M1 MCA cortex, M2 MCA cortex, M3 MCA cortex, M4 MCA cortex, and M5 MCA cortex. Each region receives a score of 1 if no ischemic changes are observed and 0 if ischemic changes are present. The total ASPECTS score ranges from 0 to 10, with 10 signifying an absence of ischemic changes and 0 indicating ischemic changes in all regions.
Another criterion is the diffusion-weighted imaging (DWI) or perfusion-weighted imaging (PWI) lesion volume, which measures the size of the ischemic tissue on magnetic resonance imaging (MRI). A larger DWI or PWI lesion volume also indicates a larger ischemic core and a higher risk of poor outcome.
The specific threshold for defining a large ischemic-core volume may vary among studies and clinical settings. In some cases, a large ischemic core may be defined as an infarct volume greater than 70 ml, while in other cases, it may be defined using the Alberta Stroke Program Early CT Score (ASPECTS) with a score of ≤ 5. A larger ischemic core is generally associated with poorer prognosis and a higher risk of complications following stroke treatment.
Current Practice Guidelines for Embolectomy in Large Ischemic Stroke
The main potential benefit of endovascular thrombectomy for patients with large ischemic strokes is to restore blood flow to the salvageable tissue (also known as the penumbra) and prevent further infarction and brain edema. This may lead to improved functional recovery and reduced mortality. Several studies have suggested that endovascular thrombectomy may be beneficial for these patients, especially if they have a favorable penumbral pattern (i.e., a small ischemic core and a large penumbra) on perfusion imaging.
Endovascular therapy (EVT) is highly recommended for acute cerebral large vessel occlusion (LVO) in patients with ASPECTS scores of ≥6 (6–10) due to occlusion of the internal carotid artery (ICA) or M1 segment of the middle cerebral artery (M1), and carries a class I recommendation from American Heart Association guideline 2018 . However, the benefits of EVT for patients with ASPECTS scores of ≤5 (0–5) are less clear, resulting in a class of recommendation IIb in the same guidelines. In real-world situations, EVT is occasionally performed on patients with ASPECTS scores between 0 and 5, as it may be effective if the penumbra area is extensive, even when early ischemic changes are widespread. Nonetheless, reperfusion therapy for patients with large ischemic cores might increase the risk of intracranial hemorrhage.
Evidence for Endovascular Thrombectomy with ASPECTS scores of ≤5
In a multicenter, open-label, randomized clinical trial in Japan that compared the outcomes of endovascular therapy plus medical care with medical care alone for 203 patients with large cerebral infarctions (ASPECTS 3-5). The study found that 31% of patients in the endovascular therapy group had a modified Rankin scale score of 0 to 3 at 90 days, compared to 12.7% in the medical care group (P=0.002). The endovascular therapy group also saw more significant improvements in NIHSS scores at 48 hours (31% vs 8.8%). However, the endovascular therapy group experienced more intracranial hemorrhages (58% vs 31.4%) .
Two recent studies published in the New England Journal of Medicine and focused on the efficacy of endovascular therapy for patients with large core infarcts. The SELECT2 trial in North America, Europe, Australia, and New Zealand, the ANGEL-ASPECT in China, and the RESCUE-Japan LIMIT trial in Japan.
The SELECT2 trial is a prospective, randomized, open-label, adaptive, international trial involving patients with large ischemic strokes due to occlusion of the internal carotid artery or the first segment of the middle cerebral artery, endovascular thrombectomy within 24 hours after onset was assessed. The trial was stopped early for efficacy, showing that endovascular thrombectomy led to better functional outcomes than medical care alone, with a generalized odds ratio of 1.51. Functional independence was achieved in 20% of thrombectomy patients compared to 7% in the medical-care group. Mortality was similar in both groups, and cerebral hemorrhages were infrequent. However, endovascular thrombectomy was associated with vascular complications .
The ANGEL-ASPECT is a multicenter, prospective, open-label, randomized trial conducted in China, 456 patients with acute large-vessel occlusion in the anterior circulation and large cerebral infarctions were studied. The trial was stopped early due to the efficacy of endovascular therapy, and results showed that endovascular therapy administered within 24 hours led to better outcomes than medical management alone (generalized odds ratio, 1.37). However, endovascular therapy was associated with more intracranial hemorrhages. Secondary outcomes generally supported the primary analysis, suggesting that in this Chinese population, endovascular therapy had benefits despite the increased risk of intracranial hemorrhage .
A meta-analysis of these three randomized control trials involving 1,011 patients was conducted (pre-print) to determine the combined benefit of endovascular thrombectomy in adult patients with large volume acute ischemic strokes and assess the risk of adverse events. The primary outcome was an overall ordinal shift across the modified Rankin scale scores toward a better outcome at 90 days. The analysis favored EVT over medical management, with a generalized odds ratio of 1.55 [95% CI 1.25 – 1.91]. However, there was a trend toward an increased risk of symptomatic intracranial hemorrhage (ICH) in the EVT group. The study concluded that EVT has a clear functional benefit for patients with large volume ischemic strokes and does not confer an increased risk of significant complications compared to medical management alone .
Roughly 20% of strokes caused by large-vessel occlusions are found to have a sizable core. In the past, patients with extensive ischemic-core volumes were often deemed unsuitable for endovascular thrombectomy and might not have been referred to facilities capable of performing this intervention. However, the results from these recent studies, which represent outcomes from diverse geographic populations not previously assessed, could advocate for expanding the eligibility criteria for thrombectomy to include patients displaying a large ischemic core in their initial imaging.
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