Stroke: Vascular and Interventional Neurology

ORIGINAL RESEARCH

Anterior Circulation Thrombectomy in

Patients With Low National Institutes of
Health Stroke Scale Score: Analysis of the
National Inpatient Sample
Karan Patel † ; Kamil Taneja † ; Liqi Shu, MD; Linda Zhang; Yunting Yu; Mohamad Abdalkader, MD;
Matthew B. Obusan; Shadi Yaghi, MD; Thanh N. Nguyen, MD; Negar Asdaghi, MD; Solomon Oak;
Daniel A. Tonetti, MD; James E. Siegler, MD

BACKGROUND: Prior studies have shown benefit for endovascular therapy (EVT) in patients with large-vessel occlusion and severe
deficits, as captured by the National Institutes of Health Stroke Scale. However the benefit of EVT in patients with National
Institutes of Health Stroke Scale score <6 is unclear.
METHODS: We queried the National Inpatient Sample (2018–2020) for patients with a large-vessel occlusion of the internal carotid
or middle cerebral artery with a National Institutes of Health Stroke Scale score <6, and compared outcomes between patients
treated with EVT versus best medical management, using propensity score matching. The primary outcome was routine dis-
charge (home or self-care). Secondary outcomes were in-hospital mortality, intracerebral hemorrhage, and length of stay. Primary
and secondary outcomes were evaluated using multivariable regression adjusted for baseline characteristics, stroke severity,
and treatment with thrombolysis.
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RESULTS: Of the 212 515 patients with an internal carotid artery/middle cerebral artery stroke, 49 115 met the inclusion criteria
for our study. A total of 8035 patients were treated with EVT, and 41 080 were treated with best medical management. Patients
treated with EVT had increased odds of routine discharge (adjusted odds ratio [OR], 1.78 [95% CI, 1.57–2.01]; P<0.001), shorter
length of hospital stays (adjusted β, −0.41 [95% CI, −0.63 to −0.19]; P<0.001), and similar rates of death (adjusted OR, 0.70
[95% CI, 0.39–1.24]; P=0.22), compared with patients treated with best medical management. These relationships persisted
in the propensity-matched cohort.
CONCLUSIONS: Patients treated with EVT compared with best medical management had greater odds of routine discharge,
reduced length of stay, and no differences in intracerebral hemorrhage or early mortality. Our findings suggest potential real-world
benefit for EVT in patients with low National Institutes of Health Stroke Scale scores.

Key Words: National Institutes of Health Stroke Scale  stroke  thrombectomy

nterior circulation strokes account for nearly endovascular therapy (EVT) in patients with disabling

A 70% of all large-vessel occlusions (LVOs). Pre-

vious clinical trials have shown benefit of
anterior circulation strokes compared with best medical
management (BMM); however, most patients treated in

Correspondence to: James E. Siegler, MD, Cooper Medical School of Rowan University, 1 Cooper Plaza, Keleman 548D, Camden, NJ 08103. E-mail:
siegler.james@gmail.com
†
K. Patel and K. Taneja contributed equally.
© 2023 The Authors. Stroke: Vascular and Interventional Neurology published by Wiley Periodicals LLC on behalf of American Heart Association and The Society for
Vascular and Interventional Neurology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits
use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Stroke: Vascular and Interventional Neurology is available at: www.ahajournals.org/journal/svin

Stroke Vasc Interv Neurol. 2023;0:e000998. DOI: 10.1161/SVIN.123.000998 1

 Patel et al
these trials presented with severe deficits and a National
Institutes of Health Stroke Scale (NIHSS) score >6.1–7
More recently, the Multicenter randomised clinical trial
of endovascular treatment of acute ischemic stroke in
the Netherlands for late arrivals (MR CLEAN-LATE) trial
investigators reported significant benefit with EVT in
patients with occlusion of the internal carotid or prox-
imal middle cerebral arteries (M1 or M2) and NIHSS
score >2. In the subgroup with NIHSS score ≤6, the
benefit of EVT over BMM was preserved, although the
95%CI crossed 1 (adjusted common odds ratio [OR],
1.79 [95% CI, 0.95–3.37]; Pinteraction =0.08). As many as
half of patients with an intracranial occlusion will have
an NIHSS score <6, with nearly one-quarter having a
proximal LVO.8 Nearly 1 in 3 patients with low NIHSS
score treated without EVT may remain dependent on
others after 3 months,9,10 and endovascular reperfusion
may be of benefit for these patients.11 In this analysis
of the US National Inpatient Sample (NIS), we used a
large population-based data set to analyze short-term
outcomes, length of hospital stay, and early mortal-
ity rates between patients with anterior-proximal LVO
treated with EVT versus BMM with NIHSS score <6.
METHODS
Data Source
All data used in this study came from the NIS. The
data are publicly available and can be found at www.
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hcup-us.ahrq.gov. Data from the NIS contain ≈20%
of all US hospitals (totaling to >7 million patients per
annum). Using complex sampling weights provided by
the Healthcare Cost and Utilization Project (HCUP),
data from the NIS can be extrapolated to the entire
US population. Any inferences drawn from these anal-
yses are representative of the US population. Because
this study uses a publicly available data set containing
only deidentified patients, it was exempt from Cooper
University Health Institutional Board Review.
Patient Population
Patients with a primary diagnosis of internal carotid
artery (ICA) or middle cerebral artery (MCA) occlusion
were identified from the NIS based on the Interna-
tional Classification of Diseases, Tenth Revision (ICD-
10), codes (I63.331, I63.41, I63.03, and I63.13). The
International Classification of Diseases, Tenth Revision,
Clinical Modification (ICD-10-CM) procedure codes
PCS 03CG3ZZ and 03CG3Z7 were used to identify
patients who underwent EVT, and they represent “extir-
pation of matter from an intracranial artery,” as they
have been used in prior analyses of the NIS.12 The
ICD-10 procedure code 3E03317 and diagnosis code
Z92.82 were used to identify patients who received
Stroke Vasc Interv Neurol. 2023;0:e000998. DOI: 10.1161/SVIN.123.000998
ICA/MCA Thrombectomy With Low NIHSS Score
Nonstandard Abbreviations and Acronyms
BMM best medical management
EVT endovascular therapy
ICH intracerebral hemorrhage
IVT intravenous thrombolysis
LVO large-vessel occlusion
mCCI modified Charlson Comorbidity Index
mRS modified Rankin Scale
NIHSS National Institutes of Health Stroke
Scale
NIS National Inpatient Sample
PS propensity score
SMD standardized mean difference
CLINICAL PERSPECTIVE
What Is New?
• Thrombectomy for anterior large-vessel occlu-
sion and low National Institutes of Health
Stroke Scale score is associated with favor-
able discharge disposition, when compared
with medical management.
What Are the Clinical Implications?
• Patients with low National Institutes of Health
Stroke Scale score may have disabling deficits
and poorer outcomes without thrombectomy.
• Low National Institutes of Health Stroke Scale
score (without considering symptom severity)
may not be a reasonable exclusion criterion for
thrombectomy.
intravenous thrombolytic treatment. Patients with an
intracranial hemorrhage were identified using the ICD-
10-CM codes I69.0 and I69.1. The inclusion criteria for
our study were admission between the years of 2018
and 2020 for those who had a primary diagnosis of
stroke attributable to ICA or MCA occlusion with an
NIHSS score <6. Only adult patients (defined as aged
≥21 years) with complete covariate information (below)
were included in the analysis. HCUP contains a uni-
form coding for race or ethnicity, where ethnicity (His-
panic) takes precedence over race. Race or ethnicity
groups coded as “Other” indicate any combination of
race or ethnicity groups, or groups which are not coded
as White, Black, Hispanic, Asian or Pacific Islander,
Native American, or are otherwise unavailable. Comor-
bidities assessed in and required by the analysis were
2
 Patel et al
hypertension, diabetes, dyslipidemia, atrial fibrillation,
overweight, coronary disease, tobacco use, and a
modified Charlson Comorbidity Index (mCCI), as has
been previously described.13 Although history of stroke
or transient ischemic attack is represented in the NIS,
these variables were excluded from the covariates for
analysis and excluded from the mCCI to reduce con-
founding given that such diagnoses may overlap with
the primary diagnosis of ICA or MCA occlusion.13
Statistical Analysis
To reduce confounding by indication for EVT, propen-
sity score (PS) matching was performed using the
nearest-neighbor method, without replacement, with
a caliper of 0.1 to create a 1:1 matched cohort of
EVT versus BMM. For each patient, a PS was calcu-
lated using a binary logistic regression model to esti-
mate the individual propensity for EVT, accounting for
age, sex, race, median household income quartile of
zip code, hospital bed size, hospital location/teaching
status, hospital region, hypertension, diabetes, dyslipi-
demia, atrial fibrillation, overweight, coronary disease,
tobacco use, mCCI, and baseline NIHSS score. Stan-
dardized mean differences (SMDs) were used to eval-
uate balance between treatment and control groups.
An SMD >[0.1] was considered to represent signifi-
cant imbalance. To ensure that our 1:1 match with the
nearest-neighbor algorithm was not biased, we repli-
Downloaded from http://ahajournals.org by on August 30, 2023
cated PS matching using radius, kernel, and local lin-
ear regression modeling to estimate the association
between EVT and the primary outcome.
The primary outcome in this study was selected
a priori as routine discharge (defined as discharge to
home or self-care). This outcome was selected as a
surrogate for good early functional outcome as it has
been strongly correlated with functional recovery in
stroke.12,14,15 Secondary outcomes in this study were
length of hospital stay (LOS), intracerebral hemorrhage
(ICH), and in-hospital mortality. ICH was selected as
a safety end point, although it is known this diag-
nosis is insensitively captured in the NIS because of
underascertainment.16 That said, we have no rea-
son to believe ICH rates would be disproportionately
coded among patients treated with EVT versus BMM.
Symptomatic ICH was not assessed because of event
rates <10 for many subgroups (also likely because
of underascertainment), which cannot be reported
per HCUP requirements. The outcomes of routine
discharge, ICH, and in-hospital mortality were analyzed
using logistic regression with adjustment for the same
covariates used in PS matching: age, sex, race, median
household income quartile of zip code, hypertension,
diabetes, dyslipidemia, atrial fibrillation, overweight,
coronary disease, tobacco use, mCCI, and NIHSS
Stroke Vasc Interv Neurol. 2023;0:e000998. DOI: 10.1161/SVIN.123.000998
ICA/MCA Thrombectomy With Low NIHSS Score
score. In addition, treatment with intravenous throm-
bolysis (IVT) was added to all multivariable models. LOS
was assessed using a multivariable linear regression
model, with adjustment for the covariates mentioned
above, including IVT.
All tests were conducted with a 2-sided significance
level of 0.05. All statistical analyses conducted in this
study were performed using STATA 17.0 (StataCorp,
College Station, TX). Patients with missing data were
excluded from the PS matching, and no imputations
were performed. No sample size calculations were per-
formed as analyses were exploratory based on available
data from the NIS.
RESULTS
Of the 1 601 840 total patients in the NIS between
2018 and 2020, 212 515 (13.2%) were diagnosed with
an ICA or MCA occlusion, and 49 115 with NIHSS
score <6 met the inclusion criteria for our study. Of
these patients, 8035 (16.4%) were treated with EVT and
41 080 (83.6%) were treated with BMM (Figure 1).
There were notable differences in baseline demo-
graphics between those treated with EVT versus BMM,
with proportionally more patients treated with BMM
having diabetes (SMD=0.14) and disproportionate
treatment across hospital regions (SMD=−0.12).
Proportionally more patients with EVT received con-
comitant IVT (SMD=−0.24) and had higher baseline
NIHSS score (SMD=−0.43), despite a maximum cutoff
of 5 for both groups. After PS matching, only con-
comitant IVT remained significantly different between
treatment groups (SMD=−0.18; Table 1).
Among unmatched patients, EVT was associated
with a higher rate of favorable outcome (routine dis-
charge) compared with BMM (56.0% versus 48.2%;
P<0.0001). A similar difference was found in PS-
matched patients (56.0% versus 44.9%; P<0.0001).
In multivariable logistic regression, treatment with EVT
was associated with an increased odds of routine
discharge (adjusted OR, 1.78 [95% CI, 1.57–2.01];
P<0.001) compared with those treated only with BMM.
This persisted with PS matching, with a similar effect
estimate (adjusted OR, 1.77 [95% CI, 1.52–2.06];
P<0.001; Table 2 and Figure 2). In the PS-matched
model for favorable outcome, other significant predic-
tors included lower NIHSS score (adjusted OR, 0.76
[95% CI, 0.72–0.80]), and mCCI of at least 3 versus
0 (adjusted OR, 0.33 [95% CI, 0.25–0.44]) and female
sex being inverse predictors (adjusted OR, 0.69 [95%
CI, 0.59–0.81]), but not IVT (adjusted OR, 1.05 [95% CI,
0.81–1.36]).
In the linear regression model for LOS, unmatched
patients who underwent EVT had a shorter LOS
3
 Patel et al ICA/MCA Thrombectomy With Low NIHSS Score
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Figure 1. Inclusion diagram. ICA/MCA indicates internal carotid artery/middle cerebral artery; NIHSS, National Institutes of Health Stroke
Scale; and NIS, National Inpatient Sample.

(adjusted β, −0.41 [95% CI, −0.63 to −0.19];
P<0.001). EVT was also associated with shorter LOS
in the PS matching group (adjusted β, −0.43 [95% CI,
−0.72 to −0.13]; P=0.005; Table 3).
For safety end points, the rate of ICH was low in
the unmatched cohort (<0.1%), and it was not signifi-
cantly different between patients treated with EVT ver-
sus BMM in the unmatched cohort (P=0.86). With PS
matching, there remained no difference in rate of ICH
(P =1.00; absolute counts not reported because of
HCUP regulations). The rate of symptomatic ICH was
low in both treatment groups; however, because of
reporting requirements of the NIS (which preclude
reporting event rates ≤10), raw counts are not pro-
vided. In unmatched patients, the overall in-hospital
mortality rate was <1%, with no difference in mor-
tality rates between patients treated with EVT ver-
sus those treated with BMM (EVT versus BMM, 0.9%

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 Patel et al ICA/MCA Thrombectomy With Low NIHSS Score

Table 1. Baseline Demographic and Clinical Variables

Unmatched cohort Propensity score–matched cohort
Best medical Best medical
management Thrombectomy management Thrombectomy
Variable (n=41 080) (n=8035) SMD (n=8035) (n=8035) SMD
Age group, n (%) 0.004 −0.06
21–44 2400 (5.8) 525 (6.5) 660 (8.2) 525 (6.5)
45–64 12 015 (29.2) 2310 (28.7) 2405 (29.9) 2310 (28.7)
≥65 26 665 (64.9) 5200 (64.7) 4970 (61.9) 5200 (64.7)
Female sex, n (%) 19 535 (47.6) 3555 (44.2) 0.07 3640 (45.3) 3555 (44.2) 0.02
Race or ethnicity, n (%) 0.02 −0.03
White 29 690 (72.3) 6085 (75.7) 6200 (77.2) 6085 (75.7)
Black 6310 (15.4) 970 (12.1) 915 (11.4) 970 (12.1)
Hispanic 2835 (6.9) 495 (6.2) 445 (5.5) 495 (6.2)
Asian/Pacific Islander 1105 (2.7) 215 (2.7) 245 (3) 215 (2.7)
Native American 155 (0.4) 30 (0.4) 35 (0.4) 30 (0.4)
Other 985 (2.4) 240 (3) 195 (2.4) 240 (3)
Median household income quartile −0.04 −0.01
of zip code, n (%)
First 11 025 (26.8) 2005 (25) 2045 (25.5) 2005 (25)
Second 10 395 (25.3) 2110 (26.3) 2160 (26.9) 2110 (26.3)
Third 10 740 (26.1) 2010 (25) 1895 (23.6) 2010 (25)
Fourth 8920 (21.7) 1910 (23.8) 1935 (24.1) 1910 (23.8)
Hospital bed size, n (%) −0.06 0.003
Small 16 980 (41.3) 3185 (39.6) 3210 (40) 3185 (39.6)
Medium 10 330 (25.1) 1905 (23.7) 1835 (22.8) 1905 (23.7)
Large 13 770 (33.5) 2945 (36.7) 2990 (37.2) 2945 (36.7)
Hospital location/teaching status, −0.03 −0.03
n (%)
Rural 9140 (22.2) 1810 (22.5) 1925 (24) 1810 (22.5)
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Urban nonteaching 10 775 (26.2) 1865 (23.2) 1815 (22.6) 1865 (23.2)
Urban teaching 21 165 (51.5) 4360 (54.3) 4295 (53.5) 4360 (54.3)
Hospital region, n (%) −0.12 0.002
Northeast 8780 (21.4) 1430 (17.8) 1385 (17.2) 1430 (17.8)
Midwest 9545 (23.2) 1845 (23) 1925 (24) 1845 (23)
South 16 325 (39.7) 3140 (39.1) 3100 (38.6) 3140 (39.1)
West 6430 (15.7) 1620 (20.2) 1625 (20.2) 1620 (20.2)
Medical history, n (%)
Hypertension 22 515 (54.8) 4540 (56.5) −0.03 4485 (55.8) 4540 (56.5) −0.01
Overweight 6960 (16.9) 1450 (18) −0.03 1490 (18.5) 1450 (18) 0.01
Atrial fibrillation 11 195 (27.3) 2410 (30) −0.06 2245 (27.9) 2410 (30) −0.05
Diabetes 14 135 (34.4) 2260 (28.1) 0.14 2245 (27.9) 2260 (28.1) −0.004
Dyslipidemia 24 800 (60.4) 4865 (60.5) −0.003 4880 (60.7) 4865 (60.5) 0.004
Coronary artery disease 9915 (24.1) 1765 (22) 0.05 1730 (21.5) 1765 (22) −0.01
Tobacco use 18 315 (44.6) 3655 (45.5) −0.02 3700 (46) 3655 (45.5) 0.01
Modified Charlson Comorbidity −0.05 −0.004
Index, n (%)
0 4815 (11.7) 830 (10.3) 825 (10.3) 830 (10.3)
1 5465 (13.3) 820 (10.2) 865 (10.8) 820 (10.2)
2 8500 (20.7) 2045 (25.5) 2005 (25) 2045 (25.5)
≥3 22 300 (54.3) 4340 (54) 4340 (54) 4340 (54)
NIHSS score, median (IQR) 2 (1–4) 3 (2–4) −0.43 3 (2–4) 3 (2–4) −0.02
Intravenous thrombolysis, n (%) 2440 (5.9) 1050 (13.1) −0.24 615 (7.7) 1050 (13.1) −0.18

IQR denotes interquartile range; NIHSS, National Institutes of Health Stroke Scale; and SMD, standardized mean difference.

Stroke Vasc Interv Neurol. 2023;0:e000998. DOI: 10.1161/SVIN.123.000998 5

 Patel et al ICA/MCA Thrombectomy With Low NIHSS Score

Table 2. Effect Estimates for Routine Discharge

Propensity score–matched
Unmatched patients patients
Logistic regression for routine
Logistic regression for routine discharge discharge
Unadjusted OR Adjusted OR Adjusted OR
Variable (95% CI) P value (95% CI) P value (95% CI) P value
Treatment
Best medical management Reference Reference Reference
Thrombectomy 1.37 (1.22–1.52) <0.001 1.78 (1.57–2.01) <0.001 1.77 (1.52–2.06) <0.001
Age group, y
21–44 Reference Reference Reference
45–64 0.67 (0.54–82) <0.001 0.69 (0.55–0.86) 0.001 0.62 (0.43–0.89) 0.01
≥65 0.23 (0.19–0.28) <0.001 0.25 (0.20–0.31) <0.001 0.22 (0.15–0.31) <0.001
Female sex 0.63 (0.58–0.68) <0.001 0.64 (0.58–0.70) <0.001 0.69 (0.59–0.81) <0.001
Race or ethnicity
White Reference Reference Reference
Black 0.94 (0.84–1.05) 0.25 0.82 (0.72–0.94) 0.005 0.88 (0.68–1.14) 0.33
Hispanic 1.16 (0.98–1.38) 0.09 1.09 (0.90–1.32) 0.37 1.10 (0.79–1.54) 0.57
Asian or Pacific Islander 1.12 (0.87–1.45) 0.38 1.18 (0.89–1.56) 0.26 1.07 (0.68–1.69) 0.77
Native American 0.87 (0.46–1.63) 0.67 0.88 (0.46–1.67) 0.69 0.87 (0.30–2.49) 0.80
Other 1.07 (0.84–1.36) 0.60 0.99 (0.75–1.31) 0.94 1.29 (0.79–2.11) 0.31
Median household income
quartile of zip code
First Reference Reference Reference
Second 1.05 (0.94–1.17) 0.39 1.07 (0.94–1.20) 0.30 1.00 (0.80–1.25) 0.99
Third 0.98 (0.88–1.09) 0.66 1.01 (0.89–1.14) 0.94 1.08 (0.87–1.35) 0.49
Fourth 1.04 (0.92–1.17) 0.53 1.05 (0.92–1.20) 0.47 1.01 (0.80–1.26) 0.96
Medical history
Hypertension 1.22 (1.13–1.33) <0.001 0.98 (0.89–1.08) 0.70 1.02 (0.87–1.20) 0.82
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Overweight 1.10 (0.99–1.23) 0.07 1.01 (0.9–1.14) 0.87 0.86 (0.70–1.06) 0.15
Atrial fibrillation 0.61 (0.56–0.67) <0.001 0.81 (0.73–0.90) <0.001 0.81 (0.68–0.96) 0.02
Diabetes 0.71 (0.65–0.78) <0.001 0.96 (0.87–1.07) 0.46 0.98 (0.82–1.18) 0.86
Hyperlipidemia 0.93 (0.86–1.01) 0.11 1.06 (0.96–1.16) 0.24 1.04 (0.89–1.22) 0.61
Coronary artery disease 0.74 (0.67–0.81) <0.001 0.97 (0.87–1.08) 0.59 1.02 (0.85–1.24) 0.80
Tobacco use 1.34 (1.24–1.44) <0.001 1.23 (1.12–1.34) <0.001 1.14 (0.98–1.32) 0.10
Modified Charlson
Comorbidity Index, n (%)
0 Reference Reference Reference
1 0.74 (0.62–0.88) <0.001 0.82 (0.68–0.98) 0.03 0.93 (0.66–1.30) 0.66
2 0.58 (0.50–0.68) <0.001 0.61 (0.52–0.71) <0.001 0.57 (0.42–0.76) <0.001
≥3 0.30 (0.26–0.34) <0.001 0.34 (0.29–0.40) <0.001 0.33 (0.25–0.44) <0.001
NIHSS score 0.74 (0.72–0.76) <0.001 0.74 (0.71–0.76) <0.001 0.76 (0.72–0.80) <0.001
Intravenous thrombolysis 0.91 (0.77–1.06) 0.24 0.99 (0.82–1.19) 0.91 1.05 (0.81–1.36) 0.72

NIHSS indicates National Institutes of Health Stroke Scale; and OR, odds ratio.

versus 1.1%; P=0.44; adjusted OR, 0.70 [95%
CI, 0.39–1.24]; P=0.22). With PS matching, there
remained no difference in in-hospital mortality (EVT ver-
sus BMM, 0.9% versus 0.1%; P=0.29; adjusted OR,
0.94 [95% CI, 0.44–2.00]; P=0.99).
Across patient subgroups, there were notable dif-
ferences in the association of EVT with favorable out-
come. With dichotomization of NIHSS score as 0 to 2
versus 3 to 5, the benefit of EVT persisted in the multi-
variable models for unmatched and matched cohorts
(Table 4), although the effect estimate was greater
for the subgroup with NIHSS score 3 to 5 versus
those with NIHSS scores 0 to 2 (Pinteraction =0.03). With
respect to IVT, the greater odds of favorable outcome
associated with EVT were only observed in patients
who did not receive IVT (PS-matched adjusted value,
1.45 [95% CI, 1.12–1.88]), whereas those treated with
IVT were at no greater odds of favorable outcome

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 Patel et al
Figure 2. Margins plots for routine discharge, with 95%
CIs. BMM indicates best medical management; EVT, endovascular
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thrombectomy; and NIHSS, National Institutes of Health Stroke Scale.
(PS-matched adjusted OR, 0.96 [95% CI, 0.57–1.60];
Pinteraction =0.03). Otherwise, the association between
EVT and favorable outcome remained preserved across
other subgroups, including age, sex, and medical
history.
The alternative PS-matching strategies (radius, ker-
nel, and local linear regression algorithms) also demon-
strated that EVT was associated with higher odds of
discharge, shorter hospital stays, and no difference in
in-hospital mortality rates (data not otherwise shown).
DISCUSSION
In this real-world analysis of patients with proximal
anterior circulation LVO with mild deficits, according to
the NIHSS (scores <6), use of EVT was associated
with better short-term functional outcomes and shorter
LOS when compared with BMM. There was no sig-
nal of harm with EVT in patients presenting with low
NIHSS scores, as the rates of in-hospital mortality and
ICH were no different between treatment groups. More
important, the NIHSS score provides a quantitative esti-
Stroke Vasc Interv Neurol. 2023;0:e000998. DOI: 10.1161/SVIN.123.000998
ICA/MCA Thrombectomy With Low NIHSS Score
mate of neurologic function but is an imperfect mea-
sure of disability. A patient may experience severe apha-
sia without weakness or vision impairment and have
a baseline NIHSS score <6. Such an aphasia may
be disabling and could potentially disqualify a patient
from EVT on the basis of simplified treatment criteria
using the NIHSS score, according to published guide-
lines from the American Heart Association/American
Stroke Association and Society of Vascular and Inter-
ventional Neurology.17,18 That said, the Society of Neu-
rointerventional Surgery recommends thrombectomy
for NIHSS score <6 when symptoms are disabling.19
In this analysis, we showed a higher rate of home dis-
charge in patients treated with EVT in patients with
low NIHSS scores, even among patients with NIHSS
scores of 0 to 2. Prior studies have been equivo-
cal in determining the benefit for EVT in this patient
population.11,20,21 The ongoing questions about EVT
efficacy may partially account for the low percentage of
patients treated with EVT in our cohort (16.3%). Despite
our analysis of a large population data set showing
benefit of EVT, we await clinical trial results for fur-
ther confirmation. At the time of this article preparation,
the ENDOLOW (Endovascular Therapy for Low NIHSS
Ischemic Strokes) and the MOSTE (Minor Stroke
Therapy Evaluation) clinical trials are set to be complete
later this year.22,23
Our findings corroborate several prior cohort stud-
ies. In 1 matched cohort study of 2 prospective reg-
istries of patients with anterior LVO and NIHSS score
<6, Haussen et al found EVT to be significantly and
independently associated with greater improvement in
NIHSS score at discharge and lower disability at dis-
charge and 3 to 6 months.9 Similarly, infarct volume
and rates of early mortality were lower with EVT in
a separate cohort reported by Abbas et al.24 That
said, larger cohort studies have failed to identify ben-
efit (or have reported harm) with EVT in patients with
low NIHSS scores.25 In the largest cohort to date,
investigators from the SSR (Swiss Stroke Registry)
used PS matching to estimate the odds of a favor-
able 90-day outcome (modified Rankin Scale [mRS]
score, 0–1) with EVT±intravenous thrombolysis ver-
sus intravenous thrombolysis alone.10 There was no
significant difference in the primary or secondary out-
comes (including mortality) with EVT when added to
intravenous thrombolysis. In contrast to that study, our
analysis included patients not treated with thrombol-
ysis and found no significant benefit of thrombolysis,
whereas thrombectomy remained significantly associ-
ated with favorable discharge. In a separate analy-
sis of overlapping years in the NIS, restricting inclu-
sion of patients to those with basilar artery occlusion
and NIHSS score <10, we also found no independent
association between intravenous thrombolysis and
7
 Patel et al ICA/MCA Thrombectomy With Low NIHSS Score

Table 3. Effect Estimates for LOS

Propensity score–matched
Unmatched patients patients
Linear regression for LOS Linear regression for LOS
Unadjusted β Adjusted β Adjusted β
Variable (95% CI) P value (95% CI) P value (95% CI) P value
Treatment
Best medical management Reference Reference Reference
Thrombectomy −0.14 (−0.35 to 0.07) 0.19 −0.41 (−0.63 to 0.19) <0.001 −0.43 (−0.72 to 0.13) 0.005
Age group, y
21–44 Reference Reference Reference
45–64 −0.03 (−0.44 to 0.37) 0.87 0.01 (−0.39 to 0.42) 0.94 0.08 (−0.57 to 0.73) 0.81
≥65 −0.24 (−0.61 to 0.12) 0.19 −0.18 (−0.56 to 0.20) 0.35 −0.29 (−0.90 to 0.32) 0.34
Female sex −0.07 (−0.24 to 0.11) 0.45 −0.08 (−0.26 to 0.10) 0.40 −0.04 (−0.34 to 0.26) 0.80
Race or ethnicity
White Reference Reference Reference
Black 0.91 (0.59 to 1.24) 0.56 (0.25 to 0.88) <0.001 0.86 (0.13 to 1.59) 0.02
Hispanic 0.44 (0.07 to 0.81) 0.02 0.28 (−0.08 to 0.64) 0.13 0.08 (−0.48 to 0.63) 0.78
Asian or Pacific Islander 0.58 (−0.04 to 1.21) 0.07 0.46 (−0.13 to 1.05) 0.13 0.63 (−0.49 to 1.76) 0.27
Native American 0.76 (−1.30 to 2.83) 0.47 0.30 (−1.67 to 2.28) 0.76 −1.03 (−2.24 to 0.18) 0.10
Other 0.96 (0.08 to 1.85) 0.03 0.79 (−0.07 to 1.65) 0.07 −0.23 (−1.04 to 0.59) 0.58
Median household income
quartile of zip code
First Reference Reference Reference
Second −0.41 (−0.68 to 0.14) 0.003 −0.25 (−0.51 to 0.01) 0.06 0.01 (−0.40 to 0.41) 0.97
Third −0.4 (−0.66 to 0.14) 0.003 −0.2 (−0.46 to 0.05) 0.11 0.15 (−0.29 to 0.59) 0.51
Fourth −0.55 (−0.81 to 0.29) <0.001 −0.28 (−0.53 to 0.03) 0.03 0.18 (−0.22 to 0.58) 0.39
Medical history
Hypertension −0.76 (0.93 to 0.59) <0.001 −0.36 (−0.55 to 0.18) <0.001 −0.30 (−0.62 to 0.01) 0.06
Overweight 0.40 (0.11 to 0.69) 0.007 0.25 (−0.03 to 0.52) 0.08 0.10 (−0.34 to 0.54) 0.65
Downloaded from http://ahajournals.org by on August 30, 2023

Atrial fibrillation 0.06 (−0.12 to 0.24) 0.51 −0.03 (−0.20 to 0.15) 0.76 −0.13 (−0.40 to 0.14) 0.35
Diabetes 0.56 (0.26 to 0.76) <0.001 −0.04 (−0.23 to 0.16) 0.73 0.26 (−0.12 to 0.64) 0.18
Hyperlipidemia −0.15 (−0.33 to 0.04) 0.11 −0.16 (−0.34 to 0.03) 0.10 −0.44 (−0.75 to 0.13) 0.006
Coronary artery disease 0.29 (0.10 to 0.49) 0.004 0.04 (−0.17 to 0.25) 0.70 0.15 (−0.24 to 0.55) 0.45
Tobacco use −0.33 (−0.50 to 0.15) <0.001 −0.39 (−0.57 to 0.22) <0.001 −0.35 (−0.66 to−0.04) 0.03
Modified Charlson Comorbidity
Index, n (%)
0 Reference Reference Reference
1 0.68 (0.46 to 0.91) <0.001 0.62 (0.39 to 0.84) <0.001 0.33 (−0.01 to 0.66) 0.06
2 0.89 (0.68 to 1.10) <0.001 0.69 (0.48 to 0.90) <0.001 0.42 (0.13 to 0.71) 0.005
≥3 2.04 (1.85 to 2.24) <0.001 1.69 (1.47 to 1.91) <0.001 1.84 (1.48 to 2.20) <0.001
NIHSS score 0.36 (0.31 to 0.42) <0.001 0.29 (0.23 to 0.34) <0.001 0.23 (0.14 to 0.33) <0.001
Intravenous thrombolysis 1.53 (1.05 to 2.01) <0.001 1.26 (0.78 to 1.74) <0.001 0.77 (0.27 to 1.27) 0.002

LOS indicates length of hospital stay; and NIHSS, National Institutes of Health Stroke Scale.

discharge to home (adjusted OR, 0.83 [95% CI, 0.40–
1.74]), although there was a significant benefit for EVT
over medical management (adjusted OR, 2.01 [95%
CI, 1.21–3.34]).12 The differences between our analy-
sis of NIS data and those from the SSR may be related
to differences in inclusion criteria (with the SSR includ-
ing only patients treated with thrombolysis), differences
in thrombectomy decision-making between US and
Swiss centers, or differences in selection of a “good out-
come” (where the SSR used 90-day mRS, whereas this
analysis of the NIS used discharge to home).
Because the data set did not contain mRS, rou-
tine discharge was used as a surrogate marker for
good functional outcomes. Prior studies have shown
that favorable discharge outcome correlates to an mRS
score of ≤2 at 90 days.26,27 In our analysis, approx-
imately half of all patients were routinely discharged
irrespective of treatment, with half being discharged to

Stroke Vasc Interv Neurol. 2023;0:e000998. DOI: 10.1161/SVIN.123.000998 8

 Patel et al ICA/MCA Thrombectomy With Low NIHSS Score

Table 4. Subgroup Analysis for the Primary Outcome Routine Discharge

Unmatched cohort Propensity score–matched cohort
Subgroup Adjusted OR (95% CI)∗ P value for interaction† Adjusted OR (95% CI)∗ P value for interaction†
NIHSS category 0.006 0.03
NIHSS score 0–2 1.55 (1.28–1.87) 1.45 (1.12–1.88)
NIHSS score 3–5 1.99 (1.70–2.33) 2.03 (1.67–2.46)
Age category, y 0.97 0.51
21–44 1.51 (0.87–2.63) 1.28 (0.66–2.48)
45–64 1.76 (1.40–2.22) 1.72 (1.30–2.28)
≥65 1.79 (1.54–2.09) 1.84 (1.51–2.23)
Sex 0.77 0.24
Female 1.76 (1.47–2.12) 1.88 (1.53–2.31)
Male 1.67 (1.50–2.11) 1.60 (1.27–2.02)
Medical history
No hypertension 1.76 (1.45–2.13) 0.15 1.83 (1.45–2.31) 0.50
Hypertension 1.77 (1.51–2.09) 1.71 (1.39–2.10)
Not overweight 1.84 (1.60–2.10) 0.22 1.82 (1.53–2.15) 0.55
Overweight 1.59 (1.17–2.15) 1.69 (1.18–2.41)
No atrial fibrillation 1.84 (1.58–2.13) 0.84 1.81 (1.51–2.18) 0.91
Atrial fibrillation 1.63 (1.30–2.04) 1.65 (1.23–2.22)
No diabetes 1.85 (1.60–2.14) 0.24 1.89 (1.58–2.27) 0.07
Diabetes 1.62 (1.30–2.03) 1.50 (1.13–1.99)
No dyslipidemia 1.93 (1.58–2.35) 0.10 2.00 (1.56–2.56) 0.30
Dyslipidemia 1.69 (1.44–1.98) 1.67 (1.36–2.04)
No coronary artery disease 1.87 (1.63–2.15) 0.58 1.90 (1.59–2.26) 0.40
Coronary artery disease 1.49 (1.16–1.92) 1.40 (1.00–1.96)
No tobacco use 1.75 (1.48–2.08) 0.80 1.55 (1.25–1.93) 0.06
Tobacco use 1.79 (1.50–2.13) 2.01 (1.61–2.50)
Modified Charlson Comorbidity Index 0.47 0.14
Downloaded from http://ahajournals.org by on August 30, 2023

0 2.79 (1.83–4.27) 3.05 (1.83–5.09)

1 1.68 (1.16–2.42) 1.32 (0.84–2.10)
2 1.66 (1.31–2.10) 1.61 (1.20–2.16)
≥3 1.66 (1.42–1.95) 1.62 (1.32–1.97)
Intravenous thrombolysis 0.47 0.01
No 1.89 (1.65–2.15) 1.92 (1.63–2.25)
Yes 1.29 (0.92–1.82) 0.96 (0.57–1.60)

NIHSS indicates National Institutes of Health Stroke Scale; and OR, odds ratio.
∗Effect estimates are adjusted for age group, sex, race group, hypertension, diabetes, dyslipidemia, atrial fibrillation, overweight, coronary disease, tobacco use,
modified Charlson Comorbidity Index, NIHSS score, and treatment with intravenous thrombolysis.
†
P values for interaction with endovascular thrombectomy are shown.

destinations where ongoing therapy and other services
are typically necessary. The relatively low rates of rou-
tine discharge (based on low NIHSS scores) in our sam-
ple may further provide evidence that NIHSS scores
should not be solely used to guide clinical decision-
making. Furthermore, an oversimplified quantification
of neurologic deficits on the basis of an NIHSS score
may confound prognostication, as patients with simi-
lar low NIHSS scores may have vastly different clinical
outcomes, depending on their symptoms. For example,
patients with similarly low NIHSS scores and deficits
in motor function had lower rates of early mortality
and morbidity compared with those who had language
and consciousness deficits, according to 1 study.28 As
such, we caution the use of the NIHSS score alone to
guide EVT decision-making.
Furthermore, in our study we found that patients
who underwent EVT had a shorter LOS (compared
with those who were treated with BMM) in both
the unmatched and matched cohorts. Previous clin-
ical trial data from Endovascular Therapy Following
Imaging Evaluation for Ischemic Stroke trial (DEFUSE-
3) showed similar findings. Patients treated with
EVT and more severe deficits had shorter LOS and
increased time at home in the first 90 days follow-
ing stroke.29 In addition, we report similar rates of
ICH and early mortality between patients receiving
EVT and BMM in our cohort, which supports the

Stroke Vasc Interv Neurol. 2023;0:e000998. DOI: 10.1161/SVIN.123.000998 9

 Patel et al
safety of this intervention in patients with low NIHSS
scores.30 The lack of signal of harm coupled with
the greater probability of a favorable discharge, and
earlier discharge, provide strong arguments to con-
sider this treatment in patients with low NIHSS scores,
particularly when symptoms may be fluctuating or
disabling.
The use of IVT among patients with low NIHSS
was not independently associated with an increased
odds of routine discharge. However, in the subgroup
of patients treated with IVT, there was no significant
benefit of EVT for the primary outcome. The greater
probability of a routine discharge was only present in
patients who did not receive IVT (Pinteraction =0.01). It is
possible that nonocclusive thrombus, small thrombus
burden, impaired microcirculation, and collateral failure
may play larger roles in infarct progression attributable
to anterior LVO when NIHSS score is low. Each of these
circumstances may respond well to systemic throm-
bolysis or endovascular recanalization of the primary
occluded vessel. The failure to confirm noninferiority of
IVT when added to EVT in patients with more disabling
deficits based on recent trial data31 does not equate
to inefficacy of IVT in proximal LVO when the NIHSS
score is low. Further studies are required before a final
determination can be made on the safety and efficacy
of IVT in this population. Other notable factors asso-
ciated with a decreased odds of favorable discharge
outcome included elderly age and higher mCCI scores.
Downloaded from http://ahajournals.org by on August 30, 2023
Elderly patients are known to have a poorer functional
reserve and, despite achieving similar reperfusion and
symptomatic ICH rates as younger counterparts, they
experience significantly poorer clinical outcomes.32 In
addition, among patients with stroke, a 1-point increase
in the Charlson Comorbidity Index has been shown to
result in a 15% increase in the odds of a poor outcome
at discharge and a 29% increase in the odds of death
by 1 year, according to prior data.33
Limitations
Despite the positive findings, our study does have
several limitations. First, the data set does not have
imaging data that may be critical in determining if
patients are candidates for EVT.34 Further elements,
such as last-well known time, time-to-arterial-puncture,
prestroke mRS score,35 and 90-day mRS score, were
not available within this data set (as such, surrogates
of mRS score were used in the analysis). In addition,
because this analysis was limited to patients with low
NIHSS score, there may be a higher rate of misclas-
sification of patients who had prior or chronic infarcts
as patients with new stroke. It is possible that many
patients included in this analysis may have had preexist-
ing deficits from a chronic occlusion, and their admis-
Stroke Vasc Interv Neurol. 2023;0:e000998. DOI: 10.1161/SVIN.123.000998
ICA/MCA Thrombectomy With Low NIHSS Score
sion NIHSS score could have represented preexisting
neurologic symptoms. That said, if symptoms asso-
ciated with the low NIHSS score predated the index
admission, such patients treated with BMM should
have been discharged with a greater frequency to home
or self-care and should have had a lower mortality rate.
However, these outcomes were not observed in the
BMM arm. Fluctuations in NIHSS score were also not
captured in the NIS, and neither were perfusion imag-
ing estimates, collateral status, more detailed occlu-
sion locations, or other indicators of tissue at risk, so
we cannot report the unique details of thrombectomy
decision-making in this cohort.
CONCLUSIONS
Overall, we found an increased odds of routine dis-
charge, decreased LOS, and similar death rates for
patients treated with EVT compared with BMM. Our
findings illustrate real-world outcomes for EVT in
patients with acute ICA/MCA occlusions who have low
NIHSS scores. We await clinical trial results to fur-
ther provide data (both clinical and imaging factors)
to determine if EVT may be beneficial in this patient
population.
ARTICLE INFORMATION
Received May 24, 2023; Accepted July 28, 2023
Affiliations
Cooper Medical School of Rowan University, Camden, NJ (K.P., L.Z., S.O.,
D.A.T., J.E.S.); Renaissance School of Medicine at Stony Brook University,
Stony Brook, NY (K.T., M.B.O.); Department of Neurology, Rhode Island Hospi-
tal, Providence, RI (L.S., S.Y., N.A.); Penn State College of Medicine, Hershey,
PA (Y.Y.); Boston Medical Center, Boston University Chobanian and Avedisian
School of Medicine, Boston, MA (M.A., T.N.N.); Cooper Neurological Institute,
Cooper University Hospital, Camden, NJ (D.A.T., J.E.S.)
Acknowledgments
None.
Sources of Funding
None.
Disclosures
T. Nguyen reports research support from SVIN and Medtronic; and advisory
board with Idorsia. The remaining authors have no disclosures.
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