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International Journal of Stroke 18(5)
Statistical analysis
Intention-to-treat (ITT) analysis will be used to analyze the
therapeutic effects of the two groups and all the data will be
analyzed with SPSS 23.0 Software. The mean ± standard
deviation (SD) will be used if the data are normally distributed,
and the median and quartile spacing (IQR) will be
used if the data are non-normally distributed. Count data
are expressed as n (%). Difference of the primary endpoint
and secondary endpoints such as mRS (0-2) at 90 days,
incidence of END, proportion of sICH within 36 h, incidence
of any cerebral hemorrhage within 36 h, and occurrence
of all-cause death in 90 days will be compared using
binary logistic regression. Distribution of mRS at 90 days
between two groups will be compared using the ordinal
logistic regression. Change in NIHSS score between two
groups will be compared using general linear model. Timeto-events
of stroke recurrence and other vascular events
will be compared using Cox regression. There is statistical
significance if p-value < 0.05.
The primary endpoint in EAST will further be stratified
by age, gender, history of stroke or transient ischemic
attack, history of hypertension, history of diabetes mellitus,
systolic blood pressure at admission (>140 mm Hg
vs ⩽140 mm Hg), time from the end of IVT to treatment
(<2h vs ⩾2 h), thrombolysis drug (tenecteplase vs
alteplase), stroke territory (anterior vs posterior circulation
infarction), and stroke etiology (large-artery atherosclerosis,
cardioembolism, small-artery occlusion, other determined
cause, and undetermined cause). Differences of
primary endpoint in above specific subgroups will be
assessed by testing for interaction of the preset baseline
variable with primary endpoint.
Study organization and funding
The protocol was designed by Hui-Sheng Chen and discussed
by the trial steering committee. Trial steering committee
is made up of external scientific advisors, and will
monitor the research and data regularly. Trial steering committee
will organize teleconference or physical meetings to
give recommendations about the trial. Neuroimaging associated
with clinical events was collected centrally and interpreted
by two independent neuroradiologists. The trial is
initiated and supported by Cerebrovascular Disease
Collaboration & Innovation Alliance (CDCIA) of Liaoning.
The antiplatelet drugs such as aspirin and clopidogrel were
donated by Shiyao Group Ouyi Pharmaceutical Co., Ltd.
Current status
At the time of the first submission of this article, the trial
does not begin to recruit the patients. Recruitment will be
continued until the complete sample size is achieved, which
is expected to be in August 2023 at the latest.
International Journal of Stroke, 18(5)
Discussion
As an effective treatment for acute ischemic stroke, IVT is
strongly recommended by guidelines, but it is mainly limited
by strict time window, low reperfusion rate, and END.
Considering that END is closely associated with vessel reocclusion,
early antiplatelet treatment seems plausible, but
antiplatelet is recommended to be administrated 24 h following
IVT by current guidelines. Previous studies have
investigated the effect of early antiplatelet (during or after
IVT) in acute ischemic stroke, but there is no definite evidence
due to the limitations of small sample size or the premature
termination resulted from high risk of sICH. Thus,
we conduct a prospective, double-blind, multicenter, randomized,
placebo-controlled study aiming to explore the
efficacy and safety of early antiplatelet in acute minor
ischemic stroke patients after IVT.
The EAST has several differences from two previous
randomized clinical trials (Supplementary sTable 3).4,9
First, the difference in neurological deficits in targeted
patients: non-minor stroke in CLEAR (NIHSS ⩾ 5)4 and
ARTIS (unrestricted NIHSS)9 versus minor stroke in
EAST (NIHSS: 0-5). Although it is still under debate
whether IVT is effective and safe for ischemic stroke
patients with mild neurological symptom, 40% ~ 50.5% of
this population received IVT in clinical practice.11,12 Given
the condition, mild stroke patients who received intravenous
thrombolysis were not ruled out in EAST trial.
Furthermore, about one-third of patients with minor stroke
harbor a large vessel occlusion and potentially develop a
medium to large infarction,13 which will attribute to END
in minor stroke.14 Thus, these patients maybe benefit from
early antiplatelet after IVT. In addition, it is well known
that higher baseline NIHSS score is a significant predictor
of sICH after IVT.15 Based on these thoughts, we infer that
minor stroke after IVT should be the best target of early
antiplatelet. Second, the difference in time points of antiplatelet
treatment: at the same time with alteplase treatment
in CLEAR4 versus within 90 min after start of
alteplase treatment in ARTIS9 versus within 6 h after the
end of alteplase or tenecteplase in EAST. We choose to
start antiplatelet treatment within 6 h after the end of IVT,
based on two considerations: (1) re-occlusion or stroke
progression mostly occurs in this time window and (2) earlier
administration such as ARTIS study may increase the
risk of sICH. Third, the difference in antithrombotic strategies:
intravenous eptifibatide in CLEAR4 versus intravenous
aspirin in ARTIS9 versus oral aspirin plus clopidogrel
in EAST. In EAST trial, aspirin plus clopidogrel was chosen
based on three reasons: (1) the dual antiplatelet has
been demonstrated to be superior to aspirin alone for
reducing the risk of minor stroke treated within 24 h after
the onset of symptoms;16,17 (2) only one time of dual antiplatelet
could avoid the possible hemorrhagic transformation
given increased risk of long-term use; and (3) oral
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