WSO - January 2024 - 18

18
International Journal of Stroke 19(1)
occlusion in treated patients (anterior circulation (internal
carotid artery (ICA), middle cerebral artery (MCA)) and/or
basilar artery), (3) time to treatment (within 8 or 24 h of
symptom onset), (4) type of comparison (matched,
unmatched, or randomized), (5) type(s) of IAT used, (6) dosage
of IAT given (if provided), and (7) timing of IAT (before
or after MT). Primary and secondary outcome data and the
sICH definitions applied in each study were also extracted.
Risk of bias assessment in studies
The quality of included observational studies5,6,12-16,20-22,25-31
was assessed by three independent reviewers (A.L., I.N.A.,
and D.K.) for risk of bias using the Newcastle-Ottawa
Quality Scale (NOS) for Cohort Studies.32 The NOS evaluates
three quality parameters (selection, comparability, and
outcome), with a maximum of 4 points for selection, 2
points for comparability, and 3 points for outcomes, with a
maximum total score of 9 for each study, representing a
good quality study.32 Studies having a total score of less
than five are identified as studies with a high risk of bias.33,34
For assessing the quality of the single randomized trial in
our study,17 we used a revised risk of bias (RoB-2) tool.35 It
evaluates the risk of bias as low, moderate, or high risk
across different parameters (such as random sequence generation,
allocation concealment, degree of blinding, attrition
bias, or selective reporting) for an overall grading of
low, moderate, or high risk of bias.
Statistical analysis
We calculated the odds ratio (OR) as effect size for each
comparison for functional independence at 90 days, allcause
mortality within 90 days, post-MT sICH, and nearcomplete
or complete recanalization. For each outcome,
comparisons were analyzed using random effects models to
account for heterogeneity, with a Mantel-Haenszel (MH)
estimator for between-study heterogeneity statistic Q, and
results displayed in forest plots. Heterogeneity was
described using I² (the percentage of the residual variation
that is attributable to between-study). We used meta-regression
to identify any heterogeneity in effect due to studylevel
covariates including the location of occlusion in
treated patients (middle cerebral artery only, middle cerebral
or internal carotid arteries, any intracranial artery, or
basilar artery only), time to treatment (⩽8 h and >8 h),
comparator group (matched, unmatched, or randomized),
and quality grade on the association between IAT and study
outcomes. We tested for the presence and extent of publication
bias using funnel plots. Adjusted effect sizes were then
estimated by incorporating theoretically missing studies
using the trim-and-fill approach.36 We performed the following
sensitivity analyses: (1) due to the presence of both
funnel plot and between-study heterogeneity, we compared
the fixed and random effects estimates of the intervention
International Journal of Stroke, 19(1)
Results
Literature search and study characteristics
A flow diagram depicting the study selection for IAT in
adjunct to MT is shown in Figure 1. A total of 1587 potentially
relevant studies were found in the search. A total of 18
studies (17 nonrandomized observational studies and 1 randomized
controlled trial) met the inclusion criteria. It is
notable that two studies were excluded one of which had too
small a sample size,23 and the other study presented results
that were not in a format that could be pooled along with the
other studies.38 A summary of study characteristics of
included studies is shown in Table 1. Primary and secondary
outcome data and definitions of sICH and successful reperfusion
of included studies are shown in Supplemental
Tables 1 and 2.
Study quality
The median quality grade was 8, with 11 studies having a
quality grade of 8 or greater for risk of bias using the NOS
scoring system5,6,12-16,20,25,29,31 (see Supplemental Tables 3
and 4). There was an overall low risk of bias using Rob-2
assessment tool for the randomized controlled trial.17 The
only potential of bias that was classified as moderate
risk was due to pre-mature terminated early during the
corona virus disease 2019 pandemic due to difficulty in
recruitment.
Effect of IAT on functional independence at 90 days
The OR for functional independence at 90 days was 1.14
(95% CI: 0.95-1.37, p = 0.17, 16 studies involving 7572
patients) with IAT with moderate between-study heterogeneity
(I2 = 38.1%; Figure 2(a)). A sizable asymmetry was
detected in the funnel plot. After applying the trim and fill
approach, the resulting adjusted OR for functional independence
at 90 days slightly increased (OR: 1.16, 95% CI:
0.96-1.40, p = 0.13; Figure 2(b)). Similar results were
observed in a fixed effect model (OR: 1.12, 95% CI: 0.97-
1.30, p = 0.13). In the meta-regression, no relationship was
identified between study-level covariates and effect size
(p > 0.05). The OR for functional independence at 90 days
with IAT was 1.28 (95% CI: 0.92-1.78, p = 0.15) in studies
effect as recommended by Sterne et al.37; (2) repeated the
analysis after only including studies that used matched or
randomized comparators; and (3) repeated the analysis
after only including studies with the highest quality score
(greater than 8). Statistical analyses were performed using
R (version 4.2.0), R package dplyr (version 1.0.9), and
meta (version 5.2-0). All estimates included a 95% confidence
interval (CI) and p values <0.05 were considered
statistically significant.
WSO - January 2024

Table of Contents for the Digital Edition of WSO - January 2024
