Endovascular thrombectomy for acute ischemic stroke with large infarct in randomized trials versus clinical practice: Comparison of the TENSION trial and the German Stroke Registry

Abstract

Background:

Randomized trials have shown that endovascular thrombectomy improves functional outcomes in patients with acute ischemic stroke and large infarct. However, there is continued debate about the generalizability of these results to routine clinical practice.

Aims:

To investigate whether functional outcomes reported in the randomized TENSION trial can be achieved in routine clinical practice.

Methods:

TENSION was a prospective, multicenter, randomized trial that enrolled patients with acute ischemic stroke and large infarct at 41 centers across Europe and Canada. Patients were randomized to endovascular thrombectomy or best medical treatment. The main inclusion criteria of TENSION were defined as pre-stroke mRS 0–2, randomization within 11 hours of symptom onset, occlusion of the intracranial ICA or M1 segment of the MCA, ASPECTS 3–5, and baseline NIHSS score 0–25. Patients from the thrombectomy arm of TENSION (TENSION-RCT) were compared to patients from the German Stroke Registry meeting the main inclusion criteria of TENSION (TENSION-GSR) using 1:1 propensity score matching. Primary outcome was the 90-day mRS score (shift analysis).

Results:

Of 308 patients who met the inclusion criteria, 198 were matched (median age, 74 [IQR, 64–81]; 98 [49.5%] female; median 90-day mRS, 5 [IQR, 3–6]). There was no significant shift in 90-day mRS scores between TENSION-RCT and TENSION-GSR (acOR, 1.19; 95% CI, 0.70–2.02; p = 0.52). The proportions of independent ambulation (90-day mRS 0–3; 33.3% vs 31.3%, p = 0.76) and severe disability or death (90-day mRS 5–6; 50.5% vs 52.5%, p = 0.78) did not differ between TENSION-RCT and TENSION-GSR.

Conclusion:

Functional outcomes of the TENSION thrombectomy arm are achievable within comprehensive stroke centers in Germany. These findings support endovascular thrombectomy for acute ischemic stroke with large infarct and its broad implementation in routine care.

Data Availability:

The data that support the findings of this study are available upon reasonable request after approval of the steering committees of the TENSION trial and the GSR-ET.

Graphical abstract

Keywords

Brain stroke ischemic stroke neurology acute stroke therapy cerebral infarction ischemia infarct thrombectomy

Introduction

Six randomized controlled trials have demonstrated that endovascular thrombectomy improves functional outcomes compared with best medical treatment in patients with acute ischemic stroke, large-vessel occlusion, and established large infarct.^1–6 These results provide strong evidence supporting the extension of endovascular thrombectomy to selected patients with acute ischemic stroke and large infarct. As a result, some clinical guidelines have been updated to recommend endovascular thrombectomy for acute ischemic stroke with large infarct in routine clinical practice, within the boundaries of the randomized controlled trial evidence.^7–9

There is continued debate about the generalizability of results from randomized trials to clinical practice.^10,11 Critics argue that the highly controlled conditions of randomized trials — characterized by strict patient selection and treatment at specialized centers — differ significantly from routine care.¹² In the context of acute stroke care, the benefit of endovascular thrombectomy may depend on factors such as center expertise, imaging capabilities, and workflow efficiency.^13,14 This may be particularly relevant for the severely affected subgroup of patients with acute ischemic stroke and large infarct.

In the thrombectomy arm of the randomized TENSION trial, 31.5% of patients achieved a modified Rankin Scale (mRS) score of 0–3 at 90 days, indicating no more than moderate disability.⁴ We aimed to assess whether the functional outcomes observed in the TENSION trial are achievable in routine clinical practice within the German healthcare system.

Methods

Study design

The study design of the randomized controlled TENSION trial has been reported in detail previously (ClinicalTrials.gov no. NCT03094715).^4,15 In summary, TENSION was an investigator-initiated, open-label, blinded-endpoint trial conducted at 41 centers across Europe and Canada between 2018 and 2023. The trial was approved by the ethics committee of the University of Heidelberg (Germany) and all participating centers. TENSION investigated the treatment effect of endovascular thrombectomy compared to best medical treatment in patients with acute ischemic stroke and large infarct. A full list of inclusion and exclusion criteria of TENSION is provided in the main publication.^4,15 The main inclusion criteria of TENSION were defined as follows: age, 18 years or older; premorbid independency, prestroke mRS score of 0–2; neurologic deficit at admission, National Institutes of Health Stroke Scale (NIHSS) score of 0–25; acute ischemic stroke due to large-vessel occlusion, M1 segment of the middle cerebral artery or intracranial segment of the internal carotid artery; large infarct at admission on non-enhanced CT or MRI, Alberta Stroke Program Early CT Score (ASPECTS) of 3–5; randomization within 11 hours of symptom onset or last known well.

The German Stroke Registry — Endovascular Treatment (GSR-ET) is an ongoing, prospective, open-label, multicenter registry which enrolled patients with acute ischemic stroke who received endovascular thrombectomy at 27 centers in Germany between 2015 and 2023 (ClinicalTrials.gov no. NCT03356392).¹⁶ The GSR-ET was approved by the ethics committee of the Ludwig Maximilian University (Germany) and all participating centers. A full list of inclusion and exclusion criteria of the GSR-ET is provided in the original publication.¹⁶

Patients from the thrombectomy arm of TENSION (TENSION-RCT) were compared with patients from the GSR-ET who met the main inclusion criteria of TENSION and were enrolled between 2015 and 2023 (TENSION-GSR). In the TENSION-GSR cohort, the TENSION time window of randomization within 11 hours of symptom onset or last known well was approximated using the time interval from symptom onset or last known well to hospital arrival, with a cutoff of 11 hours. Patients enrolled in the GSR-ET who were treated at a center participating in the TENSION trial between 2018 and 2023 were excluded from TENSION-GSR to ensure that patients were not included in both cohorts (see Figure 1).

Figure 1.

Study flowchart. The subgroup TENSION-RCT included all patients from the intention-to-treat population of the randomized controlled TENSION trial who were assigned to endovascular thrombectomy and had complete clinical data. The TENSION-GSR subgroup included all patients from the GSR-ET meeting the main inclusion criteria of TENSION. Patients from TENSION-RCT were compared to patients from TENSION-GSR using 1:1 propensity score matching. ASPECTS, Alberta Stroke Program Early CT Score; LKW, last known well; mTICI, modified Thrombolysis In Cerebral Infarction; mRS, modified Rankin Scale; NIHSS, National Institutes Health Stroke Scale; GSR-ET, German Stroke Registry—Endovascular Treatment; TENSION, The Efficacy and Safety of Thrombectomy in Stroke with extended lesion and extended time window.

This study was reported using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.¹⁷

Clinical and imaging assessment

In the TENSION trial, clinical examinations were conducted by trained investigators who were blinded to treatment allocation at baseline and at 90 days, both assessed in person. If an in-person assessment at 90 days was not possible, the mRS was assessed via telephone interview. In the GSR-ET, baseline clinical examinations were performed in person by local investigators, whereas the mRS at 90 days was assessed by trained personnel via telephone interview without blinding.

Imaging was assessed by local investigators and a central core laboratory in the TENSION trial (Eppdata, Hamburg, Germany) and by local investigators only in the GSR-ET. In TENSION-RCT, symptomatic intracranial hemorrhage at 24 hours was defined as the presence of parenchymal hemorrhage type 2 together with an increase in the NIHSS score of ⩾ 4 points or an increase in the score of an NIHSS subcategory of ⩾ 2 points. In TENSION-GSR, symptomatic intracranial hemorrhage at 24 hours was defined as the presence of any intracranial hemorrhage with an increase in the NIHSS score of ⩾ 4 points.

Outcome measures

The primary outcome was the score on the mRS at 90 days. Secondary outcomes were independent ambulation at 90 days (mRS score of 0–3) and severe disability or death at 90 days (mRS score of 5–6).

Statistical analysis

Patients from the thrombectomy arm of TENSION (TENSION-RCT) were compared to patients from the GSR-ET meeting the main inclusion criteria of TENSION (TENSION-GSR). Statistical analyses were performed using the intention-to-treat population of the TENSION trial. All analyses were performed using R statistical software (version 4.3.0, R Project for Statistical Computing) and RStudio statistical software (version 2023.03.0 + 386, Posit Software PBC). Propensity score matching was conducted using the MatchIt package in R statistical software. A two-tailed P < .05 was considered significant for all statistical tests. No adjustments were made for multiple comparisons.

Propensity score matching was applied to minimize potential selection bias and confounding in the analysis of primary and secondary outcomes (1:1 nearest-neighbor matching without replacement; caliper width of 0.2). Propensity scores were estimated using a multivariable logistic regression model, with the study setting (TENSION-RCT vs TENSION-GSR) as dependent variable and NIHSS score, time interval between symptom onset or last known well and randomization/hospital arrival, ASPECTS, and imaging modality as independent variables. Graphical comparisons were used to assess the distributional similarity of propensity scores between TENSION-RCT and TENSION-GSR after matching (see Figure S1 and Table S1).

For descriptive statistics, categorical variables were reported as the number of patients with percentages and compared between subgroups using Pearson χ2 test. Continuous variables were reported as medians with interquartile ranges (IQR) and compared between subgroups using Mann–Whitney U test after assessment for normal distribution (see Table 1 and Table S1).

Table 1.

Baseline, imaging, and treatment characteristics stratified by study setting after propensity score matching (randomized trial versus routine practice).

	After propensity score matching			P ^a
	All (n = 198)	TENSION-RCT (n = 99)	TENSION-GSR (n = 99)	P ^a
Baseline characteristics
Median age (IQR), years	74 (64–81)	74 (65–79)	74 (64–82)	.79¹
Sex				.39²
Female	98 (49.5%)	46 (46.5%)	52 (52.5%)
Male	100 (50.5%)	53 (53.5%)	47 (47.5%)
Median prestroke modified Rankin Scale (IQR)	0 (0–1)	0 (0–1)	0 (0–1)	.64¹
Median NIHSS score at hospital arrival (IQR)	18 (15–21)	18 (16–21)	18 (14–21)	.30¹
NIHSS score at hospital arrival				.89²
< 19	111 (56.1%)	55 (55.6%)	56 (56.6%)
19–25	87 (43.9%)	44 (44.4%)	43 (43.4%)
Medical history
Arterial hypertension	156 (79.6%)	79 (81.4%)	77 (77.8%)	.52²
Diabetes	38 (19.7%)	20 (21.3%)	18 (18.2%)	.59²
Dyslipidemia	76 (40.0%)	38 (41.8%)	38 (38.4%)	.64²
Median interval between symptom onset or last known well and randomization/hospital arrival, hours	4.1 (2.5–6.4)	4.1 (2.9–6.0)	4.1 (1.6–7.0)	.25¹
Interval between symptom onset or last known well and randomization/hospital arrival, hours				.35²
< 6	138 (69.7%)	72 (72.7%)	66 (66.7%)
6–11	60 (30.3%)	27 (27.3%)	33 (33.3%)
Median interval between symptom onset or last known well and groin puncture, hours^b	5.0 (3.4–7.1)	4.7 (3.4–6.5)	5.3 (3.2–8.2)	.37¹
Median interval between groin puncture and final angiogram, hours^c	0.5 (0.3–0.9)	0.5 (0.3–0.8)	0.6 (0.3–0.9)	.60¹
Imaging characteristics
Modality				.64²
CT	178 (89.9%)	88 (88.9%)	90 (90.9%)
MRI	20 (10.1%)	11 (11.1%)	9 (9.1%)
Occlusion site				.24²
Internal carotid artery	74 (37.4%)	33 (33.3%)	41 (41.4%)
Middle cerebral artery	124 (62.6%)	66 (66.7%)	58 (58.6%)
ASPECTS value, local evaluation				.80²
3	50 (25.3%)	25 (25.3%)	25 (25.3%)
4	66 (33.3%)	35 (35.4%)	31 (31.3%)
5	82 (41.4%)	39 (39.4%)	43 (43.4%)
Treatment characteristics
Intravenous alteplase administered	78 (39.4%)	44 (44.4%)	34 (34.3%)	.15²
Successful recanalization (mTICI 2b or better)	164 (82.8%)	82 (82.8%)	82 (82.8%)	> .99²
Symptomatic intracranial hemorrhage at 24 hours^d	7 (3.6%)	4 (4.0%)	3 (3.2%)	.74²

Results are reported as n (%) unless otherwise stated. National Institutes Health Stroke Scale; ASPECTS, Alberta Stroke Program Early CT Score; mTICI, modified Thrombolysis in Cerebral Infarction.

Characteristics were compared between subgroups with the use of either Kruskal–Wallis test for continuous variables (1) or Pearson’s chi-square test for categorical variables (2).

n = 98 patients in TENSION-RCT and n = 99 patients in TENSION-GSR.

n = 92 patients in TENSION-RCT and n = 91 patients in TENSION-GSR.

n = 99 patients in TENSION-RCT and n = 95 patients in TENSION-GSR.

For the primary outcome, ordinal logistic regression models were applied, with effect sizes reported as unadjusted and adjusted common odds ratios (cOR and acOR, respectively), each with corresponding 95% confidence intervals (CI) (see Table 2, Tables S2 and S3). The proportional odds assumption was met for the primary outcome analysis. For the secondary outcomes, binary logistic regression models were applied, with effect sizes reported as unadjusted and adjusted odds ratios (OR and aOR, respectively), each with corresponding 95% CI (see Table 2, Tables S2 and S3). Both the ordinal and logistic regression models were adjusted for the following covariates including the randomization stratification factors of the TENSION trial: study setting, NIHSS score, time interval between symptom onset or last known well and randomization/hospital arrival, ASPECTS, age, administration of intravenous thrombolysis, and final mTICI grade.

Table 2.

Association between study setting and functional outcomes after propensity score matching (randomized trial versus routine practice).

	After propensity score matching			P ^a	Adjusted odds ratio (95% CI)	P
	All (n = 198)	TENSION-RCT (n = 99)	TENSION-GSR (n = 99)	P ^a	Adjusted odds ratio (95% CI)	P
Primary outcome
Median modified Rankin Scale at 90 days (IQR)	5 (3–6)	5 (3–6)	5 (3–6)	.65¹	1.19 (0.70–2.02)^b	.52
Secondary outcomes
Functional independence at 90 days (modified Rankin Scale 0–2)	37 (18.7%)	18 (18.2%)	19 (19.2%)	.86²	1.01 (0.46–2.23)^c	.98
Independent ambulation at 90 days (modified Rankin Scale 0–3)	64 (32.3%)	33 (33.3%)	31 (31.3%)	.76²	1.19 (0.61–2.32)^c	.62
Severe disability or death at 90 days (modified Rankin Scale 5–6)	102 (51.5%)	50 (50.5%)	52 (52.5%)	.78²	0.87 (0.45–1.66)^c	.67
Mortality censored at 90 days (modified Rankin Scale 6)	83 (41.9%)	38 (38.4%)	45 (45.5%)	.31²	0.69 (0.37–1.29)^c	.25

Results are reported as n (%) unless otherwise stated.

Characteristics were compared between subgroups with the use of either Kruskal–Wallis test for continuous variables (1) or Pearson’s chi-square test for categorical variables (2).

Common odds ratios derived from ordinal logistic regression. Values greater than 1 indicate a shift in the distribution of modified Rankin Scale scores at 90 days toward lower values (better functional outcomes) in TENSION-RCT compared with TENSION-GSR.

Odds ratios derived from binary logistic regression. Values greater than 1 indicate an association between TENSION-RCT with better functional outcomes. TENSION-GSR was used as reference level.

Results

Study population

Patients were stratified by study setting into those enrolled in the thrombectomy arm of the randomized TENSION trial (TENSION-RCT) and those from the GSR-ET who met the main inclusion criteria of TENSION (TENSION-GSR). After 1:1 propensity score matching, a total of 198 patients were included (99 patients in TENSION-RCT and TENSION-GSR, respectively). Across all patients, the median age was 74 (IQR, 64–81), with 98 (49.5%) female and 100 (50.5%) male. The median NIHSS score on admission was 18 points (IQR, 15–21) and the median baseline ASPECTS value was 4 (IQR, 3–5). An occlusion of the internal carotid artery was present in 74 patients (37.4%), while the middle cerebral artery was occluded in 124 patients (62.6%). Intravenous thrombolysis was administered to 78 patients (39.4%). The median 90-day mRS score was 5 (IQR, 3–6) (see Figure 1 and Table 1).

Randomized trial versus routine practice

Before propensity score matching, TENSION-RCT and TENSION-GSR differed in NIHSS score, time interval between symptom onset or last known well and randomization/hospital arrival, ASPECTS, and imaging modality (see Table S1). After propensity score matching, all baseline, imaging, and treatment characteristics were balanced between TENSION-RCT and TENSION-GSR (see Table 1).

Primary outcome

Figure 2 shows the distributions of 90-day mRS scores by study setting. The median 90-day mRS score was 5 (IQR, 3–6) in TENSION-RCT and 5 (IQR, 3–6) in TENSION-GSR (Kruskal–Wallis test, p = 0.65). There was no significant shift in the distribution of 90-day mRS scores toward better functional outcomes among patients treated with endovascular thrombectomy in a randomized controlled trial compared to those treated in routine clinical practice (acOR, 1.19; 95% CI, 0.70–2.02; p = 0.52) (see Table 2 and Table S2). The results were robust, with similar effect estimates observed before and after propensity score matching (see Figure S2 and Table S3).

Figure 2.

Distribution of modified Rankin Scale scores at 90 days stratified by study setting after propensity score matching. There was no significant shift in the distribution of 90-day mRS scores toward better functional outcomes in patients treated with endovascular thrombectomy in a randomized controlled trial (TENSION-RCT) compared to those in routine clinical practice (TENSION-GSR; acOR, 1.19; 95% CI, 0.70–2.02; p = 0.52). Scores on the mRS range from 0 to 6, with 0 indicating no symptoms; 1, no clinically significant disability; 2, slight disability; 3, moderate disability (the patient is able to walk unassisted); 4, moderately severe disability; 5, severe disability; and 6, death. acOR, adjusted common odds ratio; CI, confidence interval; mRS, modified Rankin Scale.

Secondary outcomes

The percentage of patients with independent ambulation at 90 days was 33 of 99 (33.3%) in TENSION-RCT and 31 of 99 (31.3%) in TENSION-GSR (Kruskal–Wallis test, p = 0.76). Treatment within TENSION-RCT was not associated with higher odds of achieving independent ambulation at 90 days compared with treatment in TENSION-GSR (aOR, 1.19; 95% CI, 0.61–2.32; p = 0.62) (see Table 2).

Severe disability or death at 90 days was 50 of 99 (50.5%) in TENSION-RCT and 52 of 99 (52.5%) in TENSION-GSR (Kruskal–Wallis test, p = 0.78.). Odds for severe disability or death did not favor treatment in the randomized TENSION trial compared to clinical practice in the GSR-ET (acOR, 0.87; 95% CI, 0.45–1.66; p = 0.67) (see Table 2).

Discussion

Despite compelling randomized evidence demonstrating the benefit of endovascular thrombectomy in patients with acute ischemic stroke and large infarct, some clinicians remain cautious about its implementation in routine clinical practice. In this propensity score-matched analysis, functional outcomes of the TENSION thrombectomy arm were comparable with those observed in the TENSION-like cohort from the GSR-ET. No significant differences were observed in the distribution of 90-day mRS scores or in the rates of independent ambulation and severe disability or death between TENSION and the GSR-ET. The registry-based confirmation of TENSION’s functional outcomes underscores the trial’s external validity and generalizability, supporting the benefit of endovascular thrombectomy for acute ischemic stroke with large infarct in routine clinical practice beyond the controlled conditions of randomized trials.

The rate of independent ambulation at 90 days was 31.5% in the thrombectomy arm of TENSION, which was comparable with the rates reported for the thrombectomy arms of RESCUE-JAPAN LIMIT (31.0%), SELECT2 (37.9%), ANGEL-ASPECT (30.0%), LASTE¹⁸ (33.5%), and TESLA (29.8%).^1–6 These rates of independent ambulation at 90 days align with those of TENSION-like patients in the GSR-ET (31.3%) and those observed in other international observational cohorts of patients with acute ischemic stroke and large infarct treated with endovascular thrombectomy.^19–22 These consistent rates across randomized trials and observational cohorts point to the real-world effectiveness of endovascular thrombectomy for acute ischemic stroke with large infarct.

While the similarity of functional outcomes between the TENSION thrombectomy arm and routine clinical practice is reassuring, it does not imply that every patient meeting TENSION eligibility should necessarily be treated with endovascular thrombectomy. Importantly, patients with acute ischemic stroke and large infarct experience very poor functional outcomes even after endovascular thrombectomy. In the thrombectomy arm of TENSION, 49.2% of patients were either severely disabled or dead at 90 days.⁴ In addition, exclusion criteria of TENSION, such as an anticipated life expectancy of less than 6 months, consider comorbidities but cannot fully capture the complexity of real-world decision-making. Individualized decision-making remains essential in endovascular thrombectomy for acute ischemic stroke with large infarct, facilitating discussions with patients and their families about the generally poor prognosis and considering potential resource constraints within the respective healthcare system.

The treatment guidelines of the American Heart Association, the Chinese Stroke Association and the Society of Vascular and Interventional Neurology recommend endovascular thrombectomy in patients with acute ischemic stroke and large infarct meeting the inclusion and exclusion criteria of the randomized controlled trials.^7–9 However, important areas of uncertainty remain in patient selection for endovascular thrombectomy—for example, patients with very low ASPECTS 0–2, absence of arterial collaterals or perfusion mismatch, ischemic core volume greater than 150 ml, or elevated net water uptake within the infarcted tissue.^18,23–30 This study highlights the real-world applicability of the findings of the TENSION trial, and supports the need for the ongoing individual patient data meta-analysis of randomized controlled trials (ATLAS) to better define patient selection and limits of endovascular thrombectomy in acute ischemic stroke with large infarct.

Limitations

This study has several limitations. First, the retrospective study design might have introduced selection bias, particularly through the exclusion of patients with missing key variables. Although propensity score matching was used to mitigate selection bias, this approach cannot fully account for differences inherently linked to the respective study design of TENSION and GSR-ET, respectively (e.g. presence of randomization in TENSION only). Moreover, in the GSR-ET, endovascular thrombectomy for acute ischemic stroke with large infarct may have been influenced by patient characteristics not systematically captured in the registry, such as perfusion imaging parameters. Second, the observational design of the GSR-ET—without a treatment control group—does not allow estimation of treatment effects of endovascular thrombectomy in routine clinical practice, nor direct comparison with treatment effects from randomized controlled trials. Third, while the TENSION trial was stopped early for efficacy following a pre-specified interim analysis, enrollment in the GSR-ET spanned a longer period during which endovascular thrombectomy for large core infarcts was not guideline-recommended. Consequently, the limited number of patients in both cohorts precluded meaningful subgroup analyses. Fourth, interrater agreement for early ischemic signs on CT or MRI is moderate, and patient inclusion based on locally assessed ASPECTS, without confirmation by a central core laboratory, may have introduced variability and misclassification.³¹ Fifth, the GSR-ET reflects the structure and delivery of stroke care within the German healthcare system. The confirmation of TENSION’s functional outcomes in clinical practice may not translate to other healthcare systems with different organizational structures and treatment workflows.

Conclusion

Functional outcomes after endovascular thrombectomy for acute ischemic stroke with large infarct were comparable in the TENSION trial and in German clinical practice. These findings underscore that the benefits of endovascular thrombectomy for acute ischemic stroke with large infarct translate from randomized trials into clinical practice, supporting its broad implementation in routine care.

Supplemental Material

sj-pdf-1-wso-10.1177_17474930261435191 – Supplemental material for Endovascular thrombectomy for acute ischemic stroke with large infarct in randomized trials versus clinical practice: Comparison of the TENSION trial and the German Stroke Registry

Supplemental material, sj-pdf-1-wso-10.1177_17474930261435191 for Endovascular thrombectomy for acute ischemic stroke with large infarct in randomized trials versus clinical practice: Comparison of the TENSION trial and the German Stroke Registry by Laurens Winkelmeier, Fabian Flottmann, Götz Thomalla, Martin Bendszus, Helge Kniep, Matthias Bechstein, Alexander Heitkamp, Vincent Geest, Maximilian Jungnitz, Luca Meucci, Felix Schlicht, Uta Hanning, Maximilian Schell, Jens Fiehler and Christian Heitkamp in International Journal of Stroke

Footnotes

Acknowledgements

We thank the patients and their families for their participation in the TENSION trial and the GSR-ET. Participating centers and investigators of the TENSION trial are listed in Table S4. Participating centers and investigators of the GSR-ET are listed in .

TENSION Investigators

Elke R. Gizewski, Hannes Deutschmann, Michael D. Hill, Mayank Goyal, Antonín Krajina, Jan Raupach, Eva Vítková, Kateřina Vališ, Claus Ziegler Simonsen, Rolf Anker Blauenfeldt, Ronni Mikkelsen, Laurent Pierot, Paolo Pagano, Vi Tuan Hua, Fabien Subtil, Angélique Denis, Martin Bendszus, Markus A. Möhlenbruch, Christian Ulfert, Ulf Neuberger, Dominik Vollherbst, Christian Herweh, Wolfgang Wick, Silvia Schönenberger, Peter Arthur Ringleb, Fabian Flottmann, Götz Thomalla, Jens Fiehler, Maximilian Schell, Bastian Cheng, Märit Jensen, Susanne Gellißen, Eckhard Schlemm, Gernot Reimann, Nico Münnich, Andreas Kastrup, Panagiotis Papanagiotou, Fee Keil, Franziska Dorn, Gabor C. Petzold, Stefan Müller‑Hülsbeck, Silke Hopf‑Jensen, Johannes C. Gerber, Volker Puetz, Mirko Pham, Anne Hege Aamodt, Bjørn Tennøe, Kamil Zelenak, Egon Kurča, Andrej Klepanec, Jozef Haring, Blanca Fuentes.

GSR-ET Investigators

Anna Allegiani, Bernd Eckert, Joachim Rother, Georg Bohner, Christian H Nolte, Eberhard Siebert, Sarah Zweynert, Marielle Ernst, Jan Liman, Christian Riedel, Jan Borggrefe, Peter Schellinger, Jorg Berrouschot, Albrecht Bormann, Christoffer Kraemer, Ruben Muhl-Benninghaus, Jorg Hattingen, Karl‑Heinz Henn, Alexander Ludolph, Martina Petersen, Florian Stogbauer, Tobias Boeckh‑Behrens, Silke Wunderlich, Lars Kellert, Steffen Tiedt, Christoph Trumm, Jens Fiehler, Fabian Flottmann, Maximilian Schell, Gotz Thomalla, Fee Keil, Jan Hendrik Schafer, Klaus Groschel, Timo Uphaus, Arno Reich, Charlotte Weyland, Ulrike Ernemann, Sven Poli, Franziska Dorn, Gabor Petzold, Mario Abruscato, Sven Thonke.

Declaration of conflicting interests

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: L Winkelmeier: Consulting for Eppdata. F Flottmann: Consulting for Eppdata. G Thomalla: Institutional research grant from German Research Foundation, German Innovation Fund; consulting fees from AstraZeneca, Acandis, Bayer, Boehringer Ingelheim; payment for lectures from Acandis, Alexion, Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, Daiichi Sankyo, Stryker; participation on a DataSafety Monitoring Board or Advisory Board for TEA Stroke Trial; speaker of the Commission for Cerebrovascular Diseases of the German Neurological Society (DGN), member of the Board of Directors of the European Stroke Organization (ESO). M Bendszus: Institutional grants from DFG to institution; consulting for Boehringer Ingelheim, Guerbet, NeuroScios; paid lectures for Guerbet, Novartis, Seagen, Boehringer-Ingelheim. H Kniep: Consultant for Eppdata; stock or stock options in Eppdata. M Bechstein: Consulting for Eppdata. A Heitkamp: No relevant relationships. V Geest: No relevant relationships. M Jungnitz: No relevant relationships. L Meucci: No relevant relationships. F Schlicht: No relevant relationships. U Hanning: Personal fees from Eppdata and Stryker. M Schell: No relevant relationships. J Fiehler: Consulting fees from Acandis, Cerenovus, Medtronic, Microvention, Penumbra, Phenox, Roche, Stryker, TG Medical, Tonbridge; payment for lectures from Cerenovus, Medtronic, Microvention, Phenox, Tonbridge; continuation committee role for ESMINT; stock/stock option for Vastrax, Eppdata, Tegus. C Heitkamp: Consulting for Eppdata.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The TENSION trial was supported by the EU Horizon 2020 research and innovation program (754640).

ORCID iDs

Laurens Winkelmeier

Fabian Flottmann

Helge Kniep

Matthias Bechstein

Christian Heitkamp

Data availability

The data that support the findings of this study are available upon reasonable request after approval of the steering committees of the TENSION trial and the GSR-ET.

Supplemental material

Supplemental material for this article is available online.

References

Yoshimura

Sakai

Yamagami

, et al. Endovascular therapy for acute stroke with a large ischemic region. N Engl J Med 2022; 386: 1303–1313.

Sarraj

Hassan

Abraham

, et al. Trial of endovascular thrombectomy for large ischemic strokes. N Engl J Med 2023; 388: 1259–1271.

Huo

Tong

, et al. Trial of endovascular therapy for acute ischemic stroke with large infarct. N Engl J Med 2023; 388: 1272–1283.

Bendszus

Fiehler

Subtil

, et al. Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial. Lancet 2023; 402: 1753–1763.

Costalat

Jovin

Albucher

, et al. Trial of thrombectomy for stroke with a large infarct of unrestricted size. N Engl J Med 2024; 390: 1677–1689.

Investigators

TWCftT

Investigators

. Thrombectomy for stroke with large infarct on noncontrast CT: the TESLA randomized clinical trial. JAMA 2024; 332: 1355–1366.

Liu

Zhou

, et al. Chinese stroke association guidelines for clinical management of ischaemic cerebrovascular diseases: executive summary and 2023 update. Stroke Vasc Neurol 2023; 8: e3–e3.

Mokin

Jovin

Sheth

, et al. Endovascular therapy in patients with acute ischemic stroke with large infarct: a guideline from the society of vascular and interventional neurology. Stroke Vasc Interv Neurol 2025; 5: e001581.

Prabhakaran

Gonzalez

Zachrison

, et al. 2026 guideline for the early management of patients with acute ischemic stroke: a guideline from the American heart association/American stroke association. Stroke. Epub ahead of print 26 January 2026. DOI: 10.1161/STR.0000000000000513.

10.

Rothwell

. External validity of randomised controlled trials: “To whom do the results of this trial apply?”. Lancet 2005; 365: 82–93.

11.

Stuart

Bradshaw

Leaf

PJ.

Assessing the generalizability of randomized trial results to target populations. Prev Sci 2015; 16: 475–485.

12.

Ford

Norrie

Pragmatic trials. N Engl J Med 2016; 375: 454–463.

13.

Shen

Y-C

Kim

Hsia

RY.

Treatments and patient outcomes following stroke center expansion. JAMA Netw Open 2024; 7: e2444683.

14.

Saposnik

Baibergenova

O’Donnell

, et al. Hospital volume and stroke outcome. Neurology 2007; 69: 1142–1151.

15.

Bendszus

Bonekamp

Berge

, et al. A randomized controlled trial to test efficacy and safety of thrombectomy in stroke with extended lesion and extended time window. Int J Stroke 2019; 14: 87–93.

16.

Alegiani

Dorn

Herzberg

, et al. Systematic evaluation of stroke thrombectomy in clinical practice: the German stroke registry endovascular treatment. Int J Stroke 2019; 14: 372–380.

17.

Simera

Moher

Hoey

Schulz

Altman

DG.

A catalogue of reporting guidelines for health research. Eur J Clin Invest 2010; 40: 35–53.

18.

Sarraj

Hassan

Abraham

, et al. Endovascular thrombectomy for large ischemic stroke across ischemic injury and penumbra profiles. JAMA 2024; 331: 750–763.

19.

Almallouhi

Al Kasab

Hubbard

, et al. Outcomes of mechanical thrombectomy for patients with stroke presenting with low Alberta stroke program early computed tomography score in the early and extended window. JAMA Netw Open 2021; 4: e2137708.

20.

Derraz

Moulin

Gory

, et al. Endovascular thrombectomy outcomes with and without intravenous thrombolysis for large ischemic cores identified with CT or MRI. Radiology 2023; 309: e230440.

21.

Winkelmeier

Kniep

Faizy

, et al. Age and functional outcomes in patients with large ischemic stroke receiving endovascular thrombectomy. JAMA Netw Open 2024; 7: e2426007.

22.

Sarraj

Hassan

Savitz

, et al. Outcomes of endovascular thrombectomy vs medical management alone in patients with large ischemic cores: a secondary analysis of the optimizing patient’s selection for endovascular treatment in acute ischemic stroke (SELECT) study. JAMA Neurol 2019; 76: 1147–1156.

23.

Albers

Heit

Lansberg

, et al. Exploring the limits of endovascular therapy for large core patients: where do we need more data. Stroke 2024; 55: 1956–1960.

24.

Bendszus

Endovascular treatment of large core infarcts: no limits?

Clin Neuroradiol 2024; 34: 747–748.

25.

Sarraj

Campbell

BCV

. Does reperfusion benefit patients without perfusion mismatch? Stroke 2024; 55: 1326–1328.

26.

Sun

Guo

Nguyen

, et al. Alberta stroke program early computed tomography score, infarct core volume, and endovascular therapy outcomes in patients with large infarct: a secondary analysis of the ANGEL-ASPECT trial. JAMA Neurol 2024; 81: 30–38.

27.

Winkelmeier

Kniep

Thomalla

, et al. Arterial collaterals and endovascular treatment effect in acute ischemic stroke with large infarct: a secondary analysis of the TENSION trial. Radiology 2025; 314: e242401.

28.

Winkelmeier

Maros

Flottmann

, et al. Endovascular thrombectomy for large ischemic strokes with ASPECTS 0–2: a meta-analysis of randomized controlled trials. Clin Neuroradiol 2024; 34: 713–718.

29.

Liu

Abdalkader

Sang

, et al. Endovascular thrombectomy for large ischemic core stroke. Neurology 2025; 104: e213443.

30.

Ter Schiphorst

Arquizan

Labreuche

, et al. Does perfusion mismatch modify the benefit of thrombectomy in large core stroke? A meta-analysis of trials. J Neurointerv Surg. Epub ahead of print 27 November 2025. DOI: 10.1136/jnis-2025–024351.

31.

van Horn

Kniep

Broocks

, et al. ASPECTS interobserver agreement of 100 investigators from the TENSION study. Clin Neuroradiol 2021; 31: 1093–1100.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.46 MB