Thrombectomy in Extensive Stroke May Not Be Beneficial and Is Associated With Increased Risk for Hemorrhage
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Background and Purpose:
This study evaluates the benefit of endovascular treatment (EVT) for patients with extensive baseline stroke compared with best medical treatment.
This retrospective, multicenter study compares EVT and best medical treatment for computed tomography (CT)–based selection of patients with extensive baseline infarcts (Alberta Stroke Program Early CT Score ≤5) attributed to anterior circulation stroke. Patients were selected from the German Stroke Registry and 3 tertiary stroke centers. Primary functional end points were rates of good (modified Rankin Scale score of ≤3) and very poor outcome (modified Rankin Scale score of ≥5) at 90 days. Secondary safety end point was the occurrence of symptomatic intracerebral hemorrhage. Angiographic outcome was evaluated with the modified Thrombolysis in Cerebral Infarction Scale.
After 1:1 pair matching, a total of 248 patients were compared by treatment arm. Good functional outcome was observed in 27.4% in the EVT group, and in 25% in the best medical treatment group (P=0.665). Advanced age (adjusted odds ratio, 1.08 [95% CI, 1.05–1.10], P<0.001) and symptomatic intracerebral hemorrhage (adjusted odds ratio, 6.35 [95% CI, 2.08–19.35], P<0.001) were independently associated with very poor outcome. Mortality (43.5% versus 28.9%, P=0.025) and symptomatic intracerebral hemorrhage (16.1% versus 5.6%, P=0.008) were significantly higher in the EVT group. The lowest rates of good functional outcome (≈15%) were observed in groups of failed and partial recanalization (modified Thrombolysis in Cerebral Infarction Scale score of 0/1–2a), whereas patients with complete recanalization (modified Thrombolysis in Cerebral Infarction Scale score of 3) with recanalization attempts ≤2 benefitted the most (modified Rankin Scale score of ≤3:42.3%, P=0.074) compared with best medical treatment.
In daily clinical practice, EVT for CT–based selected patients with low Alberta Stroke Program Early CT Score anterior circulation stroke may not be beneficial and is associated with increased risk for hemorrhage and mortality, especially in the elderly. However, first- or second-pass complete recanalization seems to reveal a clinical benefit of EVT highlighting the vulnerability of the low Alberta Stroke Program Early CT Score subgroup.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03356392.
See related article, p 3118
Currently, 4 randomized controlled trials (RCTs; TENSION [Efficacy and Safety of Thrombectomy in Stroke With Extended Lesion and Extended Time Window: A Randomized, Controlled Trial],1 TESLA [Thrombectomy for Emergent Salvage of Large Anterior Circulation Ischemic Stroke],2 IN EXTREMIS-LASTE [Large Stroke Therapy Evaluation],3 SELECT2 [A Randomized Controlled Trial to Optimize Patient’s Selection for Endovascular Treatment in Acute Ischemic Stroke]4) are ongoing to investigate the potential benefit of endovascular treatment (EVT) in patients with extensive signs of ischemic infarction on admission.5 Nevertheless, attributed to the lower expected effect size, higher sample sizes than in previous RCTs will be needed to prove a substantial treatment effect in this subgroup.6 Additionally, based on lower incidences of low Alberta Stroke Program Early CT Score (ASPECTS) patients, and depending on the physician’s opinion on clinical equipoise, a long enrollment period can be expected.7
In past thrombectomy landmark RCTs, patients presenting with ASPECTS ≤5 were assessed based on heterogeneous imaging protocols including both computed tomography (CT) and magnetic resonance imaging for treatment selection. In the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) meta-analysis, these patients were pooled and analyzed showing a nonsignificant trend towards a treatment benefit of EVT.8 Notwithstanding the latter, this effect seems not to be valid for CT-based patient selection (Figure I in the Data Supplement),9,10 although, CT imaging represents the most frequently applied real-world modality for detection and treatment of large vessel occlusion stroke.11 Hence, currently available randomized as well as retrospective evidence (Table 1)12–20 might not be representative for a real-world setting with CT-based decision-making for EVT in patients with low ASPECTS.9 Furthermore, it remains unclear if the overall treatment effect in patients with low ASPECTS will outweigh procedure-related risks in cases where EVT is unsuccessful.20
|Study (year)||Study design||Sample size (N=)||Medical control cohort (N=)||CT-based treatment selection, % (N=)|
|Manceau et al12 (2018)||SC||82||No||MRI only|
|Mourand et al13 (2018)||SC||108||48||MRI only|
|Kaesmacher et al14 (2019)||MC||237||No||33% (78/237)|
|Kakita et al15 (2019)||MC||504||332||10% (48/504)|
|Broocks et al16 (2019)||MC||117||51||100% (117/117)|
|Jiang et al17 (2019)||MC||89||53||Both|
|Deb-Chatterji et al18 (2019)||MC||152||No||Both|
|Panni et al19 (2019)||MC||216||No||MRI only|
|Broocks et al20 (2020)||SC||170||71||100% (170/170)|
This multicenter study compares outcomes between EVT and best medical treatment (BMT) cohorts in CT-based selection of stroke patients with low ASPECTS ≤5 in a real-world setting, that is, outside of randomized trials. We hypothesized that EVT is more beneficial than BMT in this subgroup.
The deidentified data analyzed in this study will be available and shared upon reasonable request from any qualified investigator for the purpose of replicating the results after clearance by the ethics and registry committee.
All patients included in this study that received thrombectomy were enrolled in GSR-ET (German Stroke Registry—Endovascular Treatment) and treated between July 2015 and April 2018. The GSR-ET is an ongoing, open-label, prospective, multicenter registry of 25 sites in Germany collecting consecutive patients undergoing EVT. A detailed description21 and the major outcome findings of the GSR-ET study design have been published previously.22 For the comparison cohort three tertiary stroke centers (Medical Center Hamburg-Eppendorf, Germany; Hospital Bremen-Mitte, Bremen, Germany; National University Hospital Singapore, Singapore) were invited to contribute patients that underwent no EVT receiving BMT only. The main inclusion criteria for all cases were (1) CT-based diagnosis and treatment decision-making (2) of acute ischemic stroke due to anterior circulation vessel occlusions, (3) with ASPECTS 0 to 5 assessed on nonenhanced CT scans, (4) if treated endovascularly, thrombectomy was performed with approved devices, (5) if treated medically, patients with and without treatment of intravenous thrombolysis (IVT) were included based on local hospital protocols (Figure II in the Data Supplement provides a flow chart of patient inclusion criteria), (6) all patients were aged ≥18 years; there was no upper age limit. This study was prepared according to the Strengthening the Reporting of Observational Studies in Epidemiology statement (Table I in the Data Supplement).23
As the leading committee, the ethics committee of the Ludwig-Maximilians University (Munich) approved the GSR-ET. Additionally, local ethics committees of the participating hospitals gave approval as well.
Comparison of Treatment Groups
All patients that underwent EVT were compared with the BMT cohort with regard to functional outcomes and complications at 90-day follow-up. The primary functional outcomes were the rate of very poor outcome defined as a modified Rankin Scale (mRS) score of 5 to 6 and good functional outcome defined as mRS score of 0 to 3. The mRS was evaluated at 90-day follow-up by a physician or a trained and certified mRS nurse. As a subanalysis, primary functional outcomes of the EVT cohort were stratified by the degree of recanalization. Failed recanalization was defined as modified Thrombolysis in Cerebral Infarction Scale (mTICI) 0 and partial and incomplete recanalization as mTICI 1 to 2 and mTICI 2b, respectively. Accordingly, mTICI 2b was analyzed separately since its definition represents a wide range of recanalization degrees (51%–99%).11 Successful thrombectomy was defined as complete recanalization (mTICI 3). Additionally, outcome rates were subanalyzed by dichotomized subgroups of ASPECTS 0 to 3 and 4 to 5 as well as according to the number of thrombectomy maneuvers.
The secondary outcome with regard to safety was the rate of symptomatic intracranial hemorrhage (sICH) defined according to the second ECASS II (European-Australasian Acute Stroke Study) as presence of intracerebral hemorrhage and a 4-point neurological deterioration on the National Institutes of Health Stroke Scale (NIHSS).24
Standard descriptive statistics were employed for all presented data. To reduce the possibility of selection bias, a propensity score matching (PSM) was performed to adjust for covariates of baseline and procedural variables. The propensity score was estimated using a logistic regression model adjusted for the following variables: age, sex, ASPECTS on admission, NIHSS on admission, and IVT. PSM was performed based on a 1:1 pair matching without replacement using the nearest-neighbor matching algorithm with a caliper width of 0.2. Before and after matching a graphical comparison was used to assess the distributional similarity between propensity score distributions (Figure III in the Data Supplement). Furthermore, a sensitivity analysis was performed, and each covariate was plotted against the estimated propensity score, stratified by treatment status (Figure IV in the Data Supplement).
After PSM, baseline characteristics and outcome variables were compared by using the χ2 tests for categorical variables, Mann-Whitney U test (non-normally distributed data), and the unpaired Student t test (normally distributed data) for continuous variables. Univariable and stepwise multivariable logistic regression analyses were performed for very poor outcome (mRS, 5–6) and mortality, as well as sICH and good outcome (mRS, 0–3) within the endovascular cohort. Results are presented as odds ratios (OR) with 95% CI. The significance level was set at α=0.05. Statistical analyses were carried out using SPSS Version 26 (SPSS, Chicago, IL) and R (R Core Team. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing. Vienna, Austria, 2017).
Baseline and Procedural Characteristics
Before PSM both cohorts showed significant differences in baseline characteristics (Table 2) of ASPECTS (median [interquartile range], EVT: 5 [4–5], BMT: 4 [2–4], P<0.001), and NIHSS (median [interquartile range], EVT: 18 [15–21], BMT: 19 [16–23], P=0.035). Procedural characteristics showed significant differences in the number of patients receiving IVT before EVT (EVT: 53.6% versus BMT: 76.5%, P<0.001).
|Baseline, procedural, and outcome characteristics||Before propensity score matching||After propensity score matching|
|Endovascular treatment; N=168||Best medical treatment; N=264||P values||Endovascular treatment; N=124||Best medical treatment; N=124||P values|
|Median age, y (IQR)||73 (63–80)||73 (61–81)||0.709||71 (59–78)||73.5 (61–80)||0.151|
|Female sex, n (%)||69 (41.1)||118 (44.7)||0.399||51 (41.1)||56 (45.2)||0.521|
|Median admission NIHSS (IQR)||18 (15–21)||19 (16–23)||0.035||17 (14–21)||19 (15–22)||0.140|
|Median admission ASPECTS (IQR)||5 (4–5)||4 (2–4)||<0.001*||4 (3–5)||4 (3–5)||0.754|
|Median time from onset to imaging (IQR)||131 (67–194)||112 (80.5–140)||0.112||131 (67–197)||110 (78.5–139.5)||0.179|
|IVT, n (%)||90 (53.6)||202 (76.5)||<0.001*||90 (72.6)||86 (69.4)||0.576|
|sICH, n (%)||21 (12.5)||21 (8)||0.120||20 (16.1)||7 (5.6)||0.008*|
|mTICI 2b/3, n (%)||121 (72)||…||…||92 (74.2)||…||…|
|Median mRS at 90 d (IQR)||5 (3–6)||5 (4–6)†||0.954||5 (3–6)||5 (3–6)||0.266|
|mRS score 0–3, n (%)||46 (27.4)||47 (18)||0.393||34 (27.4)||31 (25)||0.665|
|mRS score 5–6, n (%)||96 (57.1)||160 (61.3)||0.391||72 (58.1)||69 (55.6)||0.701|
|Mortality n (%)||73 (43.5)||91 (34.9)||0.069||54 (43.5)||37 (29.8)||0.025*|
After PSM, 124 stroke patients in each treatment arm were analyzed and compared. All occlusions were located within the anterior circulation which involved the M1 (MT: 68.6%, 85/124; BMT: 71.8%, 89/124) or M2 segment (MT: 7.2%, 9/124; BMT: 5.6%, 7/124) of the middle cerebral artery and the terminal carotid artery (MT: 24.2%, 30/124; BMT: 22.6%, 28/124). After PSM, patients’ baseline characteristics were balanced without any significant differences (Table 2).
Within the endovascular cohort recanalization degrees were distributed as followed: 10.5% (13/124) mTICI 0, 15.3% (19/124) mTICI 1 to 2a, 40.3% (50/124) mTICI 2b, 33.9% (42) mTICI 3. The median number of thrombectomy attempts was 2 (interquartile range, 1–4).
Functional Outcome and Complications
Good functional outcome was observed in 27.4% (34/124) and 25.0% (31/124) in the EVT and BMT group (P=0.665), respectively (Figure 1). Rates of mortality (43.5%, 54/124 versus 29.8%, 37/124, P=0.025) and sICH (16.1% versus 5.6%, P=0.008) were significantly higher in the EVT group, especially in the subgroup of ASPECTS 0 to 3 (21.2% [EVT] versus 2.9% [BMT]; P=0.025; Figure V in the Data Supplement). Rates of very poor outcome (mRS score of ≥5) did not differ significantly between both treatment groups (55.6%, 69/124 versus 58.1%, 72/124, P=0.701).
There was a tendency towards significantly less cases of sICH (7.1%, 3/42) in the subgroup of mTICI 3 compared with patients that did not receive complete reperfusion (26.2% 17/65, P=0.052).
In subanalysis stratified by recanalization degree, the group of failed (mTICI 0) and partial recanalization (mTICI 1–2a) showed nonsignificantly lower rates of good functional outcome of 15.4% (2/13, P=0.734) and 15.8% (3/19, P=0.564), respectively, compared with the BMT group. Rates of very poor outcome and mortality were significantly higher in the group of failed recanalization (mTICI 0) with rates of 84.6% (11/13, P=0.044) and 69.2% (9/13, P=0.004), respectively, compared with BMT. Within groups of incomplete (mTICI 2b) and complete recanalization (mTICI 3), good functional outcome was observed in 28% (14/50, P=0.683) and 35.7% (15/42, P=0.180), respectively. With regard to the number of recanalization attempts, the subgroup of mTICI 3 with a maximum of two thrombectomy attempts showed the highest rates of good functional outcome (42.3%, 11/26) at 90 days with a trend towards significance (P=0.074) compared to BMT. There were no significant differences in the functional outcome subanalysis dichotomized by subgroups of ASPECTS 0 to 3 and 4 to 5 (Figure VI in the Data Supplement).
Multivariable Logistic Regression Analysis
In multivariable logistic regression analysis (Table 3), higher age (adjusted OR [aOR], 1.08 [95% CI, 1.05–1.10], P<0.001), ASPECTS on admission (aOR, 0.72 [95% CI, 0.55–0.93], P=0.010), and sICH (aOR, 6.35 [95% CI, 2.08–19.35], P<0.001) were independent predictors for poor outcome (mRS score of 5–6) at 90 days in all patients. Furthermore, age (aOR, 1.07 [95% CI, 1.04–1.10], P<0.001), NIHSS on admission (aOR, 1.08 [95% CI, 1.03–1.13], P=0.002), sICH (aOR, 4.39 [95% CI, 1.69–11.38], P=0.002), and EVT (aOR, 2.2 [95% CI, 1.21–3.99], P=0.009) were independently associated with death at 90 days.
|Characteristics||OR||95% CI||P value|
|Multivariable logistic regression analysis for very poor outcome|
|NIHSS on admission||…||…||0.164|
|ASPECTS on admission||0.72||0.55–0.93||0.010*|
|Multivariable logistic regression analysis for mortality|
|NIHSS on admission||1.08||1.03–1.13||0.002*|
|ASPECTS on admission||…||…||0.044†|
In the group of endovascularly treated patients, younger age (aOR, 0.93 [95% CI, 0.89–0.97] P<0.001), higher recanalization degrees (aOR, 1.45 [95% CI, 0.94–2.37] P=0.049), and cases without sICH (aOR, 0.14 [95% CI, 0.02–1.21], P=0.08) were independently associated with good outcome (mRS score of 0–3) at 90 days adjusted for covariates of sex, ASPECTS, NIHSS, and IVT (Figure 2).
Our retrospective multicenter study comparing cohorts of EVT and BMT in the setting of CT-based treatment selection for stroke patients presenting with low ASPECTS revealed several findings: (1) no general benefit of EVT over BMT was observed; (2) EVT led to significantly higher rates of sICH and mortality; (3) harmful effects of failed and partial recanalization following EVT may lead to higher rates of poor functional outcomes and mortality compared to BMT alone; (4) complete recanalization with a maximum of 2 thrombectomy attempts seems to reveal a substantial effect of EVT and thus, emphasizes technical success as a crucial mediator between benefit and harm in patients with low ASPECTS; (5) advanced age is strongly associated with poor outcomes and should be considered if intending EVT.
Given the increasing evidence that supports aggressive EVT across all subgroups, one should be aware that when treating subgroup patients outside of RCTs, complications leading to failed thrombectomy might result in harmful effects that could exceed overall treatment benefits,6 especially in daily clinical practice. Our study showed no general benefit of EVT over BMT alone in CT-based treatment decision-making for patients with low ASPECTS and was significantly associated with higher mortality. With regard to CT imaging, this finding is in line with the initial results of MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) showing no substantial benefit in the subgroup analysis of low ASPECTS patients.10 The second HERMES meta-analysis showed a promising trend towards treatment benefits of MT in patients with low ASPECTS; however, the sample size was underpowered to draw robust conclusions.8 This effect was possibly magnetic resonance imaging driven and on cases enrolled by the THRACE study (Mechanical Thrombectomy After Intravenous Alteplase Versus Alteplase Alone After Stroke). Interestingly, even the THRACE investigators did not observe a treatment effect in their initial subanalysis, whereby the question arises, how the HERMES subanalysis did show an effect (Figure I in the Data Supplement).8,25 However, no treatment effect for CT-selected cases was observed, although
HERMES core lab readers identified 34 more cases with low CT-ASPECTS.8 This highlights a fourfold problem: (1) substantial evidence of CT-selected and endovascularly treated low ASPECTS patients is currently sparse; (2) CT and magnetic resonance imaging–diffusion-weighted imaging have a poor intermodality agreement for ASPECTS reading26 and therefore, considerable differences in outcome prediction14; (3) the power of manual ASPECTS reading as a central treatment selection tool in patients with extensive baseline strokes on nonenhanced CT scans may be overestimated since the interrater agreement reliability is low and the clinical benefit of thrombectomy in low ASPECTS seems to be complexly mediated by individual factors such as preexisting diseases, age, infarct location, collaterals, and edema formation16,27–29; (4) CT-perfusion as an additional tool for treatment selection may lead to over-or underestimation of the early true infarct volume and remains a controversial modality in the light of the current debate on the infarct core concept.30–33
A post hoc analyses of the HERMES collaborators suggested that outcomes after EVT differed widely in the whole cohort when stratified by recanalization degree, even suggesting inferiority of failed recanalization compared with BMT. This was potentially attributed to procedure-related risks.34 Accordingly, we observed in a recent single-center low ASPECTS analysis that failed or incomplete recanalization did not result in worse outcomes compared to BMT.20 However, this might be explained by a previously reported single-center effect analyzing only cases from one tertiary stroke center with extensive experience in stroke care.35 On the contrary, the present study focused on large registry data also including cases from low-volume centers and observed a tendency towards inferiority in cases with failed and partial recanalization after EVT compared with BMT; however, the sample size in these subgroups was a priori underpowered to reach significance. Corroborating this finding, Kaesmacher et al14 observed in their subanalysis on CT-selected cases, only in 2 patients (2/24) a good functional outcome following unsuccessful recanalization (mTICI 0–2a). However, they reported good functional outcomes in up to 35% when thrombectomy was successful (mTICI 2b/3) in CT-selected cases. Similarly, we observed good functional outcomes in 36% of cases with mTICI 3 and even in 42% when complete recanalization was achieved with a maximum of two thrombectomy attempts. Although mortality rates were significantly higher in the EVT group, the proportions of patients with poor quality of life (mRS score of 5), which may be considered to be worse than death as a poststroke outcome, were reduced about 10% compared with the BMT group. Consequently, EVT might risk higher mortality for the sake of shifting some patients from mRS score of 5 to lower mRS scores, evoking an ethical debate about global functional outcome scales as primary study end points, with its focus on motor recovery, rather than subjective quality of life perception that immensely depends on societal and cultural differences.36,37
In comparison to HERMES meta-analysis,8 we found similar distributions of cases with sICH between both groups with significantly higher rates in the EVT cohort, especially in patients with ASPECTS 0 to 3 and a tendency towards lower incidences in completely recanalized cases as previously reported.14,38 This highlights the lack of pathophysiological understanding of cause and effect in sICH following EVT. Furthermore, multivariable logistic regression analysis revealed that the final mTICI score and the occurrence of sICH significantly impact good functional outcome. The aforementioned findings underscore the importance of technical success in EVT39,40 and reveal the vulnerability of stroke patients to potential procedure-related risks and complications, especially in low ASPECTS.8,41,42 Potential challenging interventions with high chances for failed recanalization (eg, due to vessel tortuosity) and postprocedural complications (eg, hospital-acquired infections) resulting in a poor outcome prognosis is a well-described phenomenon in EVT with an increased prevalence in very elderly patients.43,44 Accordingly, we found age independently associated with very poor outcome and mortality in both treatment arms. Thus, age as an individual baseline characteristic should be strongly considered when deciding to treat low ASPECTS patients endovascularly. Finally, the administration of bridging IVT in the setting of EVT is still a matter of current debate that is being investigated by ongoing RCTs, and this is even more controversial in patients with low ASPECTS as the evidence for IVT remains poor in this subgroup.45 Future results of stroke networks will hopefully provide further important insights into these subgroups at risk.46
Based on the absence of randomization and limited sample size, this study cannot be used to draw valid conclusions for decision-making in stroke patients with low ASPECTS. Despite using PSM to reduce the impact of potential confounding covariates, a possible selection bias cannot be ruled out due to the retrospective study design. Follow-up vessel imaging evaluating the post-treatment recanalization status was not performed in the BMT group and, therefore, was not available for further subgroup analysis and comparison.
Our study suggests no general benefit of EVT over BMT leading to high rates of mortality and sICH when treating CT-based selected patients with low ASPECTS in daily clinical practice. Failed and partial recanalization might be more harmful than BMT and thus, emphasizes the urgent need of the upcoming RCT results to define guidelines and recommendations for these critical stroke patients. Complete recanalization seems to be crucial for gaining a potential treatment benefit of EVT. Therefore, low ASPECTS patients might represent a subgroup at risk that should be treated in tertiary stroke centers with highly experienced neuro-interventionalists and neurological stroke care specialists; since these patients seem to be on the razor's edge between harm and benefit when treated endovascularly, this effect appears especially relevant in elderly patients.
Alberta Stroke Program Early CT Score
best medical treatment
European-Australasian Acute Stroke Study
German Stroke Registry—Endovascular Treatment
modified Rankin Scale
modified Thrombolysis in Cerebral Infarction Scale
National Institutes of Health Stroke Scale
symptomatic intracerebral hemorrhage
Sources of Funding
Online Figures I–VI
Online Table I
Klinikum r.d.Isar, München (Silke Wunderlich, Tobias Boeckh-Behrens), Uniklinik RWTH Aachen (Arno Reich, Martin Wiesmann), Universitätsklinik Tübingen (Ulrike Ernemann, Till-Karsten Hauser), Charité – Campus Benjamin Franklin und Campus Charité Mitte, Berlin (Eberhard Siebert, Christian Nolte), Charité - Campus Virchow Klinikum, Berlin (Sarah Zweynert, Georg Bohner), Sana Klinikum Offenbach (Alexander Ludolph, Karl-Heinz Henn), Uniklinik Frankfurt/Main (Waltraud Pfeilschifter, Marlis Wagner), Asklepios Klinik Altona, Hamburg (Joachim Röther, Bernd Eckert), Klinikum Altenburger Land (Jörg Berrouschot, Albrecht Bormann), UKE Hamburg-Eppendorf (Anna Alegiani), Uniklinik Bonn (Elke Hattingen, Gabor Petzold), Klinikum Hanau (Sven Thonke, Christopher Bangard), Klinikum Lüneburg (Christoffer Kraemer), Uniklinik München (LMU) (Martin Dichgans, Frank Wollenweber, Lars Kellert, Franziska Dorn, Moriz Herzberg), Georg-August-Universität Göttingen (Marios Psychogios, Jan Liman), Klinikum Osnabrück (Martina Petersen, Florian Stögbauer), Uniklinik Würzburg (Peter Kraft, Mirko Pham), Bezirkskrankenhaus Günzburg (Michael Braun, Gerhard F. Hamann), Universitätsmedizin Mainz (Klaus Gröschel, Timo Uphaus), Kliniken Koeln (Volker Limmroth).
Disclosures Dr Fiehler reports research support from the German Ministry of Science and Education (BMBF), German Ministry of Economy and Innovation (BMWi), German Research Foundation (DFG), European Union (EU), Hamburgische Investitions-/Förderbank (IFB), Medtronic, Microvention, Philips, Stryker; consultancy appointments; Acandis, Bayer, Boehringer Ingelheim, Cerenovus, Covidien, Evasc Neurovascular, MD Clinicals, Medtronic, Medina, Microvention, Penumbra, Route92, Stryker, Transverse Medical; stock holdings for Tegus. Dr Thomalla reports receiving consulting fees from Acandis, grant support and lecture fees from Bayer, lecture fees from Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, and Daiichi Sankyo, and consulting fees and lecture fees from Portola and Stryker. Dr Papanagiotou is a Consultant for Penumbra and Ab Medica. The other authors report no conflicts.
Bendszus M, Bonekamp S, Berge E, Boutitie F, Brouwer P, Gizewski E, Krajina A, Pierot L, Randall G, Simonsen CZ,. 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. doi: 10.1177/1747493018798558CrossrefGoogle Scholar
- 2. The TESLA trial: Thrombectomy for Emergent Salvage of Large Anterior Circulation Ischemic Stroke (TESLA).https://clinicaltrials.gov/ct2/show/NCT03805308.Google Scholar
- 3. In extremis. In extremis/moste-laste homepage.2020. https://clinicaltrials.gov/ct2/show/NCT03811769.Google Scholar
- 4. Select 2: A randomized controlled trial to optimize patient’s selection for endovascular treatment in acute ischemic stroke.https://clinicaltrials.gov/ct2/show/NCT02446587.Google Scholar
Bendszus M, Fiehler J, Thomalla G. New interventional stroke trials.Clin Neuroradiol. 2019; 29:1. doi: 10.1007/s00062-019-00763-7Google Scholar
Goyal M, Ospel JM. About antifragility and the challenge of dealing with endovascular therapy trials that fail to show a positive result.J Neurointerv Surg. 2020; 12:229–232. doi: 10.1136/neurintsurg-2019-015564Google Scholar
Ospel JM, Kashani N, Almekhlafi M, Chapot R, Goyal M. Influence of Age on EVT Treatment Decision in Patients with Low ASPECTS: results of a Multinational Survey and its Implications.Clin Neuroradiol. 2020; 30:37–40. doi: 10.1007/s00062-019-00872-3Google Scholar
Román LS, Menon BK, Blasco J, Hernández-Pérez M, Dávalos A, Majoie CBLM, Campbell BCV, Guillemin F, Lingsma H, Anxionnat R,; HERMES collaborators. Imaging features and safety and efficacy of endovascular stroke treatment: a meta-analysis of individual patient-level data.Lancet Neurol. 2018; 17:895–904. doi: 10.1016/S1474-4422(18)30242-4CrossrefMedlineGoogle Scholar
Albers GW. Endovascular thrombectomy in patients with large infarctions: reasons for restraint.Lancet Neurol. 2018; 17:836–837. doi: 10.1016/S1474-4422(18)30273-4Google Scholar
Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, Schonewille WJ, Vos JA, Nederkoorn PJ, Wermer MJ,; MR CLEAN Investigators. A randomized trial of intraarterial treatment for acute ischemic stroke.N Engl J Med. 2015; 372:11–20. doi: 10.1056/NEJMoa1411587CrossrefMedlineGoogle Scholar
Papanagiotou P, Ntaios G. Endovascular thrombectomy in acute ischemic stroke.Circ Cardiovasc Interv. 2018; 11:e005362. doi: 10.1161/CIRCINTERVENTIONS.117.005362LinkGoogle Scholar
Manceau PF, Soize S, Gawlitza M, Fabre G, Bakchine S, Durot C, Serre I, Metaxas GE, Pierot L. Is there a benefit of mechanical thrombectomy in patients with large stroke (DWI-ASPECTS ≤ 5)?Eur J Neurol. 2018; 25:105–110. doi: 10.1111/ene.13460CrossrefMedlineGoogle Scholar
Mourand I, Abergel E, Mantilla D, Ayrignac X, Sacagiu T, Eker OF, Gascou G, Dargazanli C, Riquelme C, Moynier M,. Favorable revascularization therapy in patients with ASPECTS ≤ 5 on DWI in anterior circulation stroke.J Neurointerv Surg. 2018; 10:5–9. doi: 10.1136/neurintsurg-2017-013358CrossrefMedlineGoogle Scholar
Kaesmacher J, Chaloulos-Iakovidis P, Panos L, Mordasini P, Michel P, Hajdu SD, Ribo M, Requena M, Maegerlein C, Friedrich B,. Mechanical thrombectomy in ischemic stroke patients with alberta stroke program early computed tomography score 0-5.Stroke. 2019; 50:880–888. doi: 10.1161/STROKEAHA.118.023465LinkGoogle Scholar
Kakita H, Yoshimura S, Uchida K, Sakai N, Yamagami H, Morimoto T; RESCUE-Japan Registry 2 Investigators. Impact of endovascular therapy in patients with large ischemic core: subanalysis of recovery by endovascular salvage for cerebral ultra-acute embolism Japan Registry 2.Stroke. 2019; 50:901–908. doi: 10.1161/STROKEAHA.118.024646LinkGoogle Scholar
Broocks G, Hanning U, Flottmann F, Schönfeld M, Faizy TD, Sporns P, Baumgart M, Leischner H, Schön G, Minnerup J,. Clinical benefit of thrombectomy in stroke patients with low ASPECTS is mediated by oedema reduction.Brain. 2019; 142:1399–1407. doi: 10.1093/brain/awz057CrossrefGoogle Scholar
Jiang S, Peng Y, Jing Ch, Fei Ah, Wang Hr, Gao Cj, Chen M, Li Y, Pan S. Endovascular thrombectomy can be beneficial to acute ischemic stroke patients with large infarcts. 2018; 130:1383Google Scholar
Deb-Chatterji M, Pinnschmidt H, Flottmann F, Leischner H, Broocks G, Alegiani A, Brekenfeld C, Fiehler J, Gerloff C, Thomalla G; GSR-ET Investigators. Predictors of independent outcome of thrombectomy in stroke patients with large baseline infarcts in clinical practice: a multicenter analysis.J Neurointerv Surg. 2020; 12:1064–1068. doi: 10.1136/neurintsurg-2019-015641CrossrefGoogle Scholar
Panni P, Gory B, Xie Y, Consoli A, Desilles JP, Mazighi M, Labreuche J, Piotin M, Turjman F, Eker OF,; ETIS (Endovascular Treatment in Ischemic Stroke) Investigators. Acute stroke with large ischemic core treated by thrombectomy.Stroke. 2019; 50:1164–1171. doi: 10.1161/STROKEAHA.118.024295LinkGoogle Scholar
Broocks G, Flottmann F, Schonfeld M, Bechstein M, Aye P, Kniep H, Faizy TD, McDonough R, Schon G, Deb-Chatterji M,. Incomplete or failed thrombectomy in acute stroke patients with aspects 0-5 - how harmful is trying?Eur J Neurol. 2020; 27:2031–2035. doi: 10.1111/ene.14358Google Scholar
Alegiani AC, Dorn F, Herzberg M, Wollenweber FA, Kellert L, Siebert E, Nolte CH, von Rennenberg R, Hattingen E, Petzold GC,. Systematic evaluation of stroke thrombectomy in clinical practice: the German Stroke Registry Endovascular Treatment.Int J Stroke. 2019; 14:372–380. doi: 10.1177/1747493018806199CrossrefMedlineGoogle Scholar
Wollenweber FA, Tiedt S, Alegiani A, Alber B, Bangard C, Berrouschot J, Bode FJ, Boeckh-Behrens T, Bohner G, Bormann A,. Functional outcome following stroke thrombectomy in clinical practice.Stroke. 2019; 50:2500–2506. doi: 10.1161/STROKEAHA.119.026005LinkGoogle Scholar
- 23. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, and STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.Ann Int Med. 2007; 147:573–577.CrossrefMedlineGoogle Scholar
Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, Larrue V, Bluhmki E, Davis S, Donnan G,. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators.Lancet. 1998; 352:1245–1251. doi: 10.1016/s0140-6736(98)08020-9CrossrefMedlineGoogle Scholar
Bracard S, Ducrocq X, Mas JL, Soudant M, Oppenheim C, Moulin T, Guillemin F; THRACE investigators. Mechanical thrombectomy after intravenous alteplase versus alteplase alone after stroke (THRACE): a randomised controlled trial.Lancet Neurol. 2016; 15:1138–1147. doi: 10.1016/S1474-4422(16)30177-6CrossrefMedlineGoogle Scholar
McTaggart RA, Jovin TG, Lansberg MG, Mlynash M, Jayaraman MV, Choudhri OA, Inoue M, Marks MP, Albers GW; DEFUSE 2 Investigators. Alberta stroke program early computed tomographic scoring performance in a series of patients undergoing computed tomography and MRI: reader agreement, modality agreement, and outcome prediction.Stroke. 2015; 46:407–412. doi: 10.1161/STROKEAHA.114.006564LinkGoogle Scholar
Meyer L, Schönfeld M, Bechstein M, Hanning U, Cheng B, Thomalla G, Schön G, Kemmling A, Fiehler J, Broocks G. Ischemic lesion water homeostasis after thrombectomy for large vessel occlusion stroke within the anterior circulation: the impact of age.J Cereb Blood Flow Metab. 2021; 41:45–52. doi: 10.1177/0271678X20915792Google Scholar
Broocks G, Kniep H, Schramm P, Hanning U, Flottmann F, Faizy T, Schönfeld M, Meyer L, Schön G, Aulmann L,. Patients with low Alberta Stroke Program Early CT Score (ASPECTS) but good collaterals benefit from endovascular recanalization.J Neurointerv Surg. 2020; 12:747–752. doi: 10.1136/neurintsurg-2019-015308CrossrefGoogle Scholar
van Horn N, Kniep H, Broocks G, Meyer L, Flottmann F, Bechstein M, Götz J, Thomalla G, Bendszus M, Bonekamp S,. Aspects interobserver agreement of 100 investigators from the tension study [published online January 27, 2021].Clin Neuroradiol. 2021. doi: 10.1007/s00062-020-00988-xGoogle Scholar
Martins N, Aires A, Mendez B, Boned S, Rubiera M, Tomasello A, Coscojuela P, Hernandez D, Muchada M, Rodríguez-Luna D,. Ghost infarct core and admission computed tomography perfusion: redefining the role of neuroimaging in Acute Ischemic Stroke.Interv Neurol. 2018; 7:513–521. doi: 10.1159/000490117Google Scholar
Goyal M, Ospel JM, Menon B, Almekhlafi M, Jayaraman M, Fiehler J, Psychogios M, Chapot R, van der Lugt A, Liu J,. Challenging the ischemic core concept in acute ischemic stroke imaging.Stroke. 2020; 51:3147–3155. doi: 10.1161/STROKEAHA.120.030620LinkGoogle Scholar
Ernst M, Boers AMM, Aigner A, Berkhemer OA, Yoo AJ, Roos YB, Dippel DWJ, van der Lugt A, van Oostenbrugge RJ, van Zwam WH,; MR CLEAN Trial Investigators (www.mrclean-trial.org). Association of computed tomography ischemic lesion location with functional outcome in acute large vessel occlusion ischemic stroke.Stroke. 2017; 48:2426–2433. doi: 10.1161/STROKEAHA.117.017513LinkGoogle Scholar
McDonough R, Elsayed S, Faizy TD, Austein F, Sporns PB, Meyer L, Bechstein M, van Horn N, Nawka MT, Schon G,. Computed tomography-based triage of extensive baseline infarction: aspects and collaterals versus perfusion imaging for outcome prediction [published online November 9, 2020].J Neurointerv Surg. 2020:neurintsurg-2020-016848. doi: 10.1136/neurintsurg-2020-016848Google Scholar
Liebeskind DS, Bracard S, Guillemin F, Jahan R, Jovin TG, Majoie CB, Mitchell PJ, van der Lugt A, Menon BK, San Román L,; HERMES Collaborators. eTICI reperfusion: defining success in endovascular stroke therapy.J Neurointerv Surg. 2019; 11:433–438. doi: 10.1136/neurintsurg-2018-014127CrossrefMedlineGoogle Scholar
Kim BM, Baek JH, Heo JH, Kim DJ, Nam HS, Kim YD. Effect of cumulative case volume on procedural and clinical outcomes in endovascular thrombectomy.Stroke. 2019; 50:1178–1183. doi: 10.1161/STROKEAHA.119.024986LinkGoogle Scholar
Broocks G, Fiehler J, Meyer L. Letter by broocks et al regarding article, “mechanical thrombectomy in patients with ischemic stroke with prestroke disability”.Stroke. 2020; 51:e167–e168. 10.1161/STROKEAHA.120.030269LinkGoogle Scholar
Rahme R, Zuccarello M, Kleindorfer D, Adeoye OM, Ringer AJ. Decompressive hemicraniectomy for malignant middle cerebral artery territory infarction: is life worth living?J Neurosurg. 2012; 117:749–754. doi: 10.3171/2012.6.JNS111140CrossrefMedlineGoogle Scholar
Wang DT, Churilov L, Dowling R, Mitchell P, Yan B. Successful recanalization post endovascular therapy is associated with a decreased risk of intracranial haemorrhage: a retrospective study.BMC Neurol. 2015; 15:185. doi: 10.1186/s12883-015-0442-xGoogle Scholar
Flottmann F, Leischner H, Broocks G, Nawabi J, Bernhardt M, Faizy TD, Deb-Chatterji M, Thomalla G, Fiehler J, Brekenfeld C. Recanalization rate per retrieval attempt in mechanical thrombectomy for acute ischemic stroke.Stroke. 2018; 49:2523–2525. doi: 10.1161/STROKEAHA.118.022737LinkGoogle Scholar
Nikoubashman O, Dekeyzer S, Riabikin A, Keulers A, Reich A, Mpotsaris A, Wiesmann M. True first-pass effect.Stroke. 2019; 50:2140–2146. doi: 10.1161/STROKEAHA.119.025148LinkGoogle Scholar
Kaesmacher J, Kaesmacher M, Maegerlein C, Zimmer C, Gersing AS, Wunderlich S, Friedrich B, Boeckh-Behrens T, Kleine JF. Hemorrhagic transformations after thrombectomy: risk factors and clinical relevance.Cerebrovasc Dis. 2017; 43:294–304. doi: 10.1159/000460265CrossrefMedlineGoogle Scholar
Nawabi J, Kniep H, Schön G, Flottmann F, Leischner H, Kabiri R, Sporns P, Kemmling A, Thomalla G, Fiehler J,. Hemorrhage after endovascular recanalization in acute stroke: lesion extent, collaterals and degree of ischemic water uptake mediate tissue vulnerability.Front Neurol. 2019; 10:569. doi: 10.3389/fneur.2019.00569Google Scholar
Meyer L, Alexandrou M, Flottmann F, Deb-Chatterji M, Abdullayev N, Maus V, Politi M, Bernkopf K, Roth C, Kastrup A,; German Stroke Registry–Endovascular Treatment (GSR-ET) †. Endovascular treatment of very elderly patients aged ≥90 with acute ischemic stroke.J Am Heart Assoc. 2020; 9:e014447. doi: 10.1161/JAHA.119.014447LinkGoogle Scholar
Meyer L, Broocks G, Bechstein M, Flottmann F, Leischner H, Brekenfeld C, Schön G, Deb-Chatterji M, Alegiani A, Thomalla G,; German Stroke Registry – Endovascular Treatment (GSR – ET). Early clinical surrogates for outcome prediction after stroke thrombectomy in daily clinical practice.J Neurol Neurosurg Psychiatry. 2020; 91:1055–1059. doi: 10.1136/jnnp-2020-323742CrossrefGoogle Scholar
Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, Boysen G, Bluhmki E, Höxter G, Mahagne MH. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS).JAMA. 1995; 274:1017–1025.CrossrefMedlineGoogle Scholar
Broderick JP, Palesch YY, Janis LS; National Institutes of Health StrokeNet Investigators. The National Institutes of Health StrokeNet: a User’s Guide.Stroke. 2016; 47:301–303. doi: 10.1161/STROKEAHA.115.011743LinkGoogle Scholar