Author: Märit Jensen, MD

University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Clinical Stroke and Imaging Research (CSI) group

Twitter: @maeritjensen

Mechanical thrombectomy, when performed within 24 hours after symptom onset in patients with small-to-moderate acute ischemic strokes due to an occlusion of a large vessel, has been shown to significantly improve functional outcome at 90 days. The results of previous trials, however, do not apply to patients with large strokes, which until now mostly have been excluded from treatment. Just recently, two trials on endovascular therapy for acute ischemic stroke with large infarct have demonstrated evidence of a benefit in this subgroup of patients.

We talked about the results and clinical implications of ANGEL-ASPECT1 and SELECT22, both published in the NEJM a few days ago, with Prof Götz Thomalla who is the neurological PI of the TENSION trial.

Märit Jensen: Many thanks for taking the time for this interview. What is your opinion, will ANGEL-ASPECT and SELECT2 have an impact on clinical practice of thrombectomy?

Götz Thomalla: Indeed, I am pretty sure that the results of these trials will change clinical practice. The publication of the two trials has immediately stimulated lively discussions among stroke physicians around the world. From now on, there is no longer a reason to withhold thrombectomy in patients with large vessel occlusion based on large ischemic core. In many cases, this will make treatment decisions easier.


MJ: Both trials randomized patients with large ischemic core up to 24 hours to either thrombectomy or medical management. ANGEL-ASPECT enrolled 456 patients and SELECT2 enrolled 352 patients. Can you briefly summarize the results of the trials?

GT: Results were straight-forward and similar in both trials: Thrombectomy was associated with a higher odds ratio for better functional outcome assessed by the mRS at 90 days (ANGEL-ASPECT: OR 1.37 [95% CI 1.11-1.69]; SELECT2: OR 1.51 [95% 1.20-1.89]). Mortality was similar among treatment groups and there was no excess of symptomatic intracranial hemorrhage with thrombectomy. In brief, thrombectomy is safe and effective even in patients with large core.


MJ: SELECT2 was conducted at sites across the US, Canada, Europe, Australia, and New Zealand, while ANGEL-ASPECT was exclusively involved Chinese sites. What are the differences between both trials?

GT: There are some differences in design and results. The definition of a large ischemic core differed slightly. ANGEL-ASPECT used the definition of ASPECTS 3-5 or core volume of 70-100 ml. In SELECT2, the definition was ASPECTS 3-5 or core volume >50 ml. Both trials mainly enrolled patients with occlusion of the M1 or the intracranial internal carotid artery. Patients in SELECT2 had more severe strokes reflected by a median NIHSS of 19 as compared to 15-16 in ANGEL-ASPECT.

There were also differences in outcomes, as overall patients in ANGEL-ASPECT showed better outcomes. In SELECT2, rates of functional independence (mRS 0-2) wer 20% in the thrombectomy group and 7% in the medical-care group. In the Chinese trial, functional independence was achieved by 30% vs. 11%. Mortality was higher in SELECT2 (38% vs. 42%) than in ANGEL-ASPECT (22% vs. 20%). In SELECT2, up to 20% of patients had procedure-related complications, such as dissection, vasospasms, or vessel perforation. As to medical management, in both trials rates of intravenous thrombolysis were rather low, approximately 20% in SELECT2 and less than 30% in ANGEL-ASPECT. Despite differences both trials were consistent in the clear benefit of thrombectomy over medical management alone.

MJ: Did the subgroup analyses provide additional insights?

GT: The analysis of subgroups did not bring any surprises. Subgroup analysis in both trials were supportive and consistent with the main findings. There was no significant heterogeneity of the treatment effect for any relevant subgroup, but, of course, both trials were not powered for subgroup analysis.


MJ: You are involved in the TENSION study which addresses a very similar clinical question. Will these results influence your trial?

GT: This is a good question, and within the TENSION team we have asked ourselves this question immediately. The TENSION Steering Committee had an ad hoc meeting after the trial results were published. As of now, TENSION has randomized 252 patients. We decided to suspend randomization in TENSION until the results of ANGEL-ASPECT and SELECT2 have been discussed by our DSMB, which will meet by the end of February. At that time, we will also have the results of a pre-planned interim analysis of the first 222 patients randomized in TENSION available, and based on the recommendations of the DSMB, the Steering Committee will then make a final decision.


MJ: It appears, as if the most burning scientific questions concerning stroke thrombectomy have been answered, including thrombectomy for basilar artery occlusion, and just now also for large core. What is next to come?

GT: This is another good question. It remains to be elucidated, whether thrombectomy is also effective in distal occlusions, e.g., M3, A2, P2 and beyond, and we are looking forward to the results of the DISTAL trial. With the momentum stemming from of ESCAPE-NA13, I also expect further trials of neuroprotection or other add-on treatments together with endovascular stroke treatment. Maybe the results of the recently completed ESCAPE-NEXT trial will be presented at ESOC 2023 in Munich. Finally, probably the most important next step will be to transfer these findings from clinical trials into guidelines and clinical practice and make this effective treatment available to as many patients as possible across the world.


  1. Huo X, Ma G, Tong X, Zhang X, Pan Y, Nguyen TN, et al. Trial of endovascular therapy for acute ischemic stroke with large infarct. New England Journal of Medicine. 2023
  2. Sarraj A, Hassan AE, Abraham MG, Ortega-Gutierrez S, Kasner SE, Hussain MS, et al. Trial of endovascular thrombectomy for large ischemic strokes. New England Journal of Medicine. 2023
  3. Hill MD, Goyal M, Menon BK, Nogueira RG, McTaggart RA, Demchuk AM, et al. Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (escape-na1): A multicentre, double-blind, randomised controlled trial. Lancet. 2020;395:878-887

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