Stroke

CLINICAL AND POPULATION SCIENCES

Thrombectomy in Extensive Stroke May Not Be

Beneficial and Is Associated With Increased Risk
for Hemorrhage
Lukas Meyer , MD; Matthias Bechstein , MD; Maxim Bester , MD; Uta Hanning, MD, MHBA; Caspar Brekenfeld, MD;
Fabian Flottmann, MD; Helge Kniep , MD; Noel van Horn , MD; Milani Deb-Chatterji , MD; Götz Thomalla, MD;
Peter Sporns, MD, MHBA; Leonard Leong-Litt Yeo, MD; Benjamin Yong-Qiang Tan, MD; Anil Gopinathan, MD, MBBS;
Andreas Kastrup, MD; Maria Politi, MD; Panagiotis Papanagiotou, MD; André Kemmling, MD, MHBA; Jens Fiehler , MD;
Gabriel Broocks, MD; for the German Stroke Registry–Endovascular Treatment (GSR-ET)*

BACKGROUND AND PURPOSE: This study evaluates the benefit of endovascular treatment (EVT) for patients with extensive
baseline stroke compared with best medical treatment.

METHODS: 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.
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RESULTS: 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.

CONCLUSIONS: 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.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03356392.

GRAPHIC ABSTRACT: An online graphic abstract is available for this article.

Key Words: hemorrhage ◼ risk ◼ stroke ◼ thrombectomy

Correspondence to: Lukas Meyer, MD, Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Germany,
Martinistrasse 52, 20246 Hamburg, Germany. Email lu.meyer@uke.de
*A list of all German Stroke Registry–Endovascular Treatment (GSR-ET) members is given in the Appendix.
The Data Supplement is available with this article at https://www.ahajournals.org/doi/suppl/10.1161/STROKEAHA.120.033101.
For Sources of Funding and Disclosures, see page 3115.
© 2021 American Heart Association, Inc.
Stroke is available at www.ahajournals.org/journal/str

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 Meyer et al
CLINICAL AND POPULATION
Nonstandard Abbreviations and Acronyms
SCIENCES
ASPECTS Alberta Stroke Program Early CT Score
BMT best medical treatment
CT computed tomography
ECASS II European-Australasian Acute Stroke Study
EVT endovascular treatment
GSR-ET German Stroke Registry—Endovascular
Treatment
IVT intravenous thrombolysis
mRS modified Rankin Scale
mTICI modified Thrombolysis in Cerebral
Infarction Scale
NIHSS National Institutes of Health Stroke Scale
sICH symptomatic intracerebral hemorrhage
C
urrently, 4 randomized controlled trials (RCTs; TEN-
SION [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
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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 clin-
ical equipoise, a long enrollment period can be expected.7
See related article, p 3118
In past thrombectomy landmark RCTs, patients pre-
senting with ASPECTS ≤5 were assessed based on het-
erogeneous 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 treat-
ment benefit of EVT.8 Notwithstanding the latter, this
effect seems not to be valid for CT-based patient selec-
tion (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 ran-
domized as well as retrospective evidence (Table 1)12–20
3110   October 2021
Treatment of Large Baseline Strokes
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 over-
all treatment effect in patients with low ASPECTS will
outweigh procedure-related risks in cases where EVT is
unsuccessful.20
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.
METHODS
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.
Study Cohort
All patients included in this study that received thrombec-
tomy 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 consecu-
tive 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 endovascu-
larly, thrombectomy was performed with approved devices, (5) if
treated medically, patients with and without treatment of intrave-
nous 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 hospi-
tals 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
Stroke. 2021;52:3109–3117. DOI: 10.1161/STROKEAHA.120.033101
 Meyer et al Treatment of Large Baseline Strokes

Table 1. Current Evidence of Endovascular Treatment for Stroke Patients With Low ASPECTS

CLINICAL AND POPULATION

≤5 in Nonrandomized Retrospective Studies With Regard to CT-Based Therapy Selection

Sample size Medical control CT-based treatment

SCIENCES
Study (year) Study design (N=) cohort (N=) 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 al (2019)
17
MC 89 53 Both
Deb-Chatterji et al18 (2019) MC 152 No Both
Panni et al19 (2019) MC 216 No MRI only
Broocks et al (2020)
20
SC 170 71 100% (170/170)

ASPECTS indicates Alberta Stroke Program Early CT Scores; CT, computed tomography; MRI, magnetic resonance imaging;
MS, multicenter; and SC, single-center.

subanalysis, primary functional outcomes of the EVT cohort
were stratified by the degree of recanalization. Failed recan-
alization was defined as modified Thrombolysis in Cerebral
Infarction Scale (mTICI) 0 and partial and incomplete recanali-
zation as mTICI 1 to 2 and mTICI 2b, respectively. Accordingly,
mTICI 2b was analyzed separately since its definition repre-
sents a wide range of recanalization degrees (51%–99%).11
Successful thrombectomy was defined as complete recanaliza-
tion (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
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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).
RESULTS
Baseline and Procedural Characteristics
Before PSM both cohorts showed significant differ-
ences in baseline characteristics (Table 2) of ASPECTS

(median [interquartile range], EVT: 5 [4–5], BMT: 4 [2–4],

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
Statistical Analysis
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 base-
line and procedural variables. The propensity score was estimated
using a logistic regression model adjusted for the following vari-
ables: 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 com-
parison 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 covari-
ate was plotted against the estimated propensity score, stratified
by treatment status (Figure IV in the Data Supplement).
After PSM, baseline characteristics and outcome vari-
ables 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 endo-
vascular cohort. Results are presented as odds ratios (OR)
P<0.001), and NIHSS (median [interquartile range],
EVT: 18 [15–21], BMT: 19 [16–23], P=0.035). Proce-
dural characteristics showed significant differences in
the number of patients receiving IVT before EVT (EVT:
53.6% versus BMT: 76.5%, P<0.001).
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 throm-
bectomy 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)

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 Meyer et al Treatment of Large Baseline Strokes

Table 2. Patients’ Baseline, Procedural, and Outcome Characteristics Compared in Both Treatment Cohorts Before and After
CLINICAL AND POPULATION

Propensity Score Matching

Before propensity score matching After propensity score matching

SCIENCES

Baseline, procedural, and outcome Endovascular Best medical Endovascular Best medical
characteristics treatment; N=168 treatment; N=264 P values treatment; N=124 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*

ASPECTS indicates Alberta Stroke Program Early CT Score; IQR, interquartile range; IVT, Intravenous Thrombolysis; mRS, modified Rankin Scale; mTICI, modified
Thrombolysis in Cerebral Infarction Scale; NIHSS, National Institutes of Health Stroke Scale; and sICH, symptomatic intracerebral hemorrhage.
*Significant values.
†For 3 patients mRS at 90 days was not available.

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 Supple-
ment). 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).
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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

There was a tendency towards significantly less cases mortality were significantly higher in the group of
of sICH (7.1%, 3/42) in the subgroup of mTICI 3 com- failed recanalization (mTICI 0) with rates of 84.6%
pared with patients that did not receive complete reper- (11/13, P=0.044) and 69.2% (9/13, P=0.004),
fusion (26.2% 17/65, P=0.052). respectively, compared with BMT. Within groups of

Figure 1. Comparison of modified Rankin Scale (mRS) scores between both treatment cohorts stratified by recanalization
degrees after propensity score matching.
BMT indicates best MT; MT, medical treatment; mTICI, modified Thrombolysis in Cerebral Infarction Scale; and sICH, symptomatic intracerebral
hemorrhage.

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 Meyer et al Treatment of Large Baseline Strokes

incomplete (mTICI 2b) and complete recanalization In the group of endovascularly treated patients,

CLINICAL AND POPULATION

(mTICI 3), good functional outcome was observed younger age (aOR, 0.93 [95% CI, 0.89–0.97] P<0.001),
in 28% (14/50, P=0.683) and 35.7% (15/42, higher recanalization degrees (aOR, 1.45 [95% CI,

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 signifi-
cant 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 pre-
dictors 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.
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SCIENCES
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).
DISCUSSION
Our retrospective multicenter study comparing cohorts of
EVT and BMT in the setting of CT-based treatment selec-
tion 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 techni-
cal 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 aggres-
sive EVT across all subgroups, one should be aware that
when treating subgroup patients outside of RCTs, com-

Table 3. Multivariable Logistic Regression Analysis for

Independent Predictors of Very Poor Outcome (mRS Score plications leading to failed thrombectomy might result
of 5–6) and Mortality at 90-Day Follow-Up Within the Whole in harmful effects that could exceed overall treatment
Study Population Regardless of Treatment Arm benefits,6 especially in daily clinical practice. Our study
Characteristics OR 95% CI P value
showed no general benefit of EVT over BMT alone in
CT-based treatment decision-making for patients with
Multivariable logistic regression analysis for very poor outcome
low ASPECTS and was significantly associated with
Age, y 1.08 1.05–1.10 <0.001*
higher mortality. With regard to CT imaging, this finding
Sex (male) … … 0.919
is in line with the initial results of MR CLEAN (Multi-
NIHSS on admission … … 0.164 center Randomized Clinical Trial of Endovascular Treat-
ASPECTS on admission 0.72 0.55–0.93 0.010* ment for Acute Ischemic Stroke in the Netherlands)
IVT … … 0.470 showing no substantial benefit in the subgroup analy-
sICH 6.35 2.08–19.35 0.001* sis of low ASPECTS patients.10 The second HERMES
EVT … … 0.544 meta-analysis showed a promising trend towards treat-
Multivariable logistic regression analysis for mortality
ment benefits of MT in patients with low ASPECTS;
Age, y 1.07 1.04–1.10 <0.001*
however, the sample size was underpowered to draw
robust conclusions.8 This effect was possibly magnetic
Sex (male) … … 0.611
resonance imaging driven and on cases enrolled by the
NIHSS on admission 1.08 1.03–1.13 0.002*
THRACE study (Mechanical Thrombectomy After Intra-
ASPECTS on admission … … 0.044† venous Alteplase Versus Alteplase Alone After Stroke).
IVT … … 0.407 Interestingly, even the THRACE investigators did not
sICH 4.39 1.69–11.38 0.002* observe a treatment effect in their initial subanalysis,
EVT 2.2 1.21–3.99 0.009* whereby the question arises, how the HERMES sub-
ASPECTS indicates Alberta Stroke Program Early CT Score; EVT, endovascu-
analysis did show an effect (Figure I in the Data Supple-
lar treatment; IVT, intravenous thrombolysis; mRS, modified Rankin Scale; NIHSS, ment).8,25 However, no treatment effect for CT-selected
National Institutes of Health Stroke Scale; OR, odds ratio; and sICH, symptomatic cases was observed, although HERMES core lab read-
intracerebral hemorrhage.
*Significant values.
ers identified 34 more cases with low CT-ASPECTS.8 This
†Not selected in the last step of the regression model. highlights a fourfold problem: (1) substantial evidence of

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 Meyer et al
CLINICAL AND POPULATION
SCIENCES
Figure 2. Forest plot based on stepwise multivariable regression analysis for independent predictors of good functional
outcome (modified Rankin Scale [mRS] 0–3) at 90 d within the endovascular treatment after propensity score adjusted
for covariates (sex, Alberta Stroke Program Early CT Scores, National Institutes of Health Stroke Scale, and intravenous
thrombolysis).
mTICI indicates modified Thrombolysis in Cerebral Infarction Scale; and sICH, symptomatic intracerebral hemorrhage.
CT-selected and endovascularly treated low ASPECTS
patients is currently sparse; (2) CT and magnetic reso-
nance imaging–diffusion-weighted imaging have a poor
intermodality agreement for ASPECTS reading26 and
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therefore, considerable differences in outcome predic-
tion14; (3) the power of manual ASPECTS reading as a
central treatment selection tool in patients with exten-
sive 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 loca-
tion, collaterals, and edema formation16,27–29; (4) CT-per-
fusion 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 recanaliza-
tion 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-cen-
ter 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 regis-
try data also including cases from low-volume centers
3114   October 2021
Treatment of Large Baseline Strokes
and observed a tendency towards inferiority in cases
with failed and partial recanalization after EVT com-
pared with BMT; however, the sample size in these
subgroups was a priori underpowered to reach signifi-
cance. 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 percep-
tion 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
Stroke. 2021;52:3109–3117. DOI: 10.1161/STROKEAHA.120.033101
 Meyer et al
a tendency towards lower incidences in completely
recanalized cases as previously reported.14,38 This high-
lights 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 signif-
icantly impact good functional outcome. The aforemen-
tioned findings underscore the importance of technical
success in EVT39,40 and reveal the vulnerability of stroke
patients to potential procedure-related risks and com-
plications, especially in low ASPECTS.8,41,42 Poten-
tial 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 out-
come 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 cur-
rent 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 hope-
fully provide further important insights into these sub-
groups at risk.46
Downloaded from http://ahajournals.org by on July 9, 2023
Limitations
Based on the absence of randomization and limited
sample size, this study cannot be used to draw valid con-
clusions 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.
Conclusions
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 recanaliza-
tion seems to be crucial for gaining a potential treat-
ment benefit of EVT. Therefore, low ASPECTS patients
might represent a subgroup at risk that should be
Stroke. 2021;52:3109–3117. DOI: 10.1161/STROKEAHA.120.033101
Treatment of Large Baseline Strokes
treated in tertiary stroke centers with highly experi-
CLINICAL AND POPULATION
enced neuro-interventionalists and neurological stroke
care specialists; since these patients seem to be on the
SCIENCES
razor's edge between harm and benefit when treated
endovascularly, this effect appears especially relevant
in elderly patients.
ARTICLE INFORMATION
Received October 16, 2020; final revision received March 9, 2021; accepted
April 9, 2021.
Affiliations
Department of Diagnostic and Interventional Neuroradiology (L.M., M. Bechstein,
M. Bester, U.H., C.B., F.F., H.K., N.v.H., P.S., J.F., G.B.) and Department of Neu-
rology (M.D.-C., G.T.), University Medical Center Hamburg-Eppendorf, Hamburg,
Germany. Department of Diagnostic and Interventional Neuroradiology, University
Hospital Basel, Switzerland (P.S.). Department of Neuroradiology, Westpfalz-Klini-
kum, Kaiserslautern, Germany (A. Kemmling). Department of Diagnostic and In-
terventional Neuroradiology, University Medical Center Marburg, Marburg Univer-
sity, Germany (A. Kemmling). Department of Neurology, Hospital Bremen-Mitte,
Bremen, Germany (A. Kastrup). Department of Diagnostic and Interventional
Neuroradiology, Hospital Bremen-Mitte, Germany (M.P., P.P.). Areteion University
Hospital, National and Kapodistrian University of Athens, Greece (P.P.). Division
of Neurology, Department of Medicine, National University Health System, Singa-
pore, Singapore (L.L.-L.Y., B.Y.-Q.T.). Division of Interventional Radiology, Depart-
ment of Diagnostic Imaging, National University Hospital, Singapore, Singapore
(A.G.). Yong Loo Lin School of Medicine, National University of Singapore, Singa-
pore, Singapore (L.L.-L.Y., B.Y.-Q.T., A.G.).
Sources of Funding
None.
Disclosures
Dr Fiehler reports research support from the German Ministry of Science and
Education (BMBF), German Ministry of Economy and Innovation (BMWi), Ger-
man Research Foundation (DFG), European Union (EU), Hamburgische Inves-
titions-/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 re-
ports 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.
Supplemental Materials
Online Figures I–VI
Online Table I
APPENDIX
GSR-ET Collaborators
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), Chari-
té - 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 Ban-
gard), Klinikum Lüneburg (Christoffer Kraemer), Uniklinik München (LMU) (Mar-
tin 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).
October 2021   3115
 Meyer et al
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