Reperfusing Large Core Stroke

Patients with large-core infarcts have been excluded from early trials on endovascular treatment, mainly in relation to safety issues. However, as techniques and approaches become more and more sophisticated, there seems to be room for treating also patients with large core infarcts.

The Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism Japan Large IscheMIc core Trial (RESCUE Japan LIMIT) was the first to challenge the preconception of futile recanalization in large core stroke.[1] Among 202 randomized patients, with MRI for evaluation, mechanical thrombectomy doubled the rate of good functional outcome (90-day mRS 0–2) compared with medical management (14% vs 7.8%). Such trend was also confirmed for mRS 0-3, prompting interim analysis for other ongoing trials.

The RCT to Optimize Patient’s Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT2) trial, counting on a prevalent CT-based triage, showed similar results to RESCUE JAPAN. Specificly, patients with ASPECTS 3–5 or CT perfusion volume >50 mL reached a 20% chance of good functional outcome with thrombectomy, as compared to 7% only in medical arm.[2]

The Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusion Patients with a Large Infarct Core (ANGEL- ASPECT) trial, a large China-based trial, further reinforced the concept.[3] Terminated early, the RCT showed that thrombectomy carried a good functional outcome rate of 30% versus 11.6% for medical arm. What is more, thrombectomy also almost halved mRS 5 rates, suggesting a potential positive cost-effective result when implemented in practice.

The MAGNA individual-patient data meta-analysis have been presented at ESOC 2023.[4] Collecting more than 1000 patients from available RCTs, MAGNA showed a consistent benefit of thrombectomy over medical management for large core ischemic stroke across ASPECTS 3, 4 and 5, and with cores ranging <70ml up to 149ml. Overall, rates of good functional outcome doubled with thrombectomy compared to medical management. The benefit of thrombectomy seems therefore to extend to large core stroke. Further studies will refine our approach, and guidelines will take into account a bulk of new evidence. In the meantime we should consider frailty, tolerance of disability and comorbidities to weigh our approach, taking into account that the magnitude of treatment effect seems solid. A final thought is for cost-effectiveness, as number needed to treat may be influenced by abovementioned factors and age as well, in a global aging population. ---  References:

1. Yoshimura, S.; Sakai, N.; Yamagami, H.; Uchida, K.; Beppu, M.; Toyoda, K.; Matsumaru, Y.; Matsumoto, Y.; Kimura, K.; Takeuchi, M.; et al. Endovascular Therapy for Acute Stroke with a Large Ischemic Region. N. Engl. J. Med. 2022, 386, 1303–1313, doi:10.1056/nejmoa2118191.
2. Sarraj, A.; Hassan, A.E.; Abraham, M.G.; Ortega-Gutierrez, S.; Kasner, S.E.; Hussain, M.S.; Chen, M.; Blackburn, S.; Sitton, C.W.; Churilov, L.; et al. Trial of Endovascular Thrombectomy for Large Ischemic Strokes. N. Engl. J. Med. 2023, 388, 1259–1271, doi:10.1056/NEJMoa2214403.
3. Huo, X.; Ma, G.; Tong, X.; Zhang, X.; Pan, Y.; Nguyen, T.N.; Yuan, G.; Han, H.; Chen, W.; Wei, M.; et al. Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct. N. Engl. J. Med. 2023, 388, 1272–1283, doi:10.1056/NEJMoa2213379.
4. Online reference – https://twitter.com/StrokeAHA_ASA/status/1662023765889351683