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Articles

CAST: randomised placebo-controlled trial of early aspirin use in


20 000 patients with acute ischaemic stroke
CAST (Chinese Acute Stroke Trial) Collaborative Group*

Summary Introduction
During the current decade in China there will be about 15
Background Aspirin is effective in the treatment of acute
million deaths from stroke, plus much disability.1 Although
myocardial infarction and in the long-term prevention of
the proportion of haemorrhagic strokes is somewhat higher
serious vascular events in sur vivors of stroke and
than in western populations, ischaemic stroke still accounts
myocardial infarction. There is, however, no reliable
for the majority of new cases and deaths in China.2,3 If a
evidence on the effectiveness of early aspirin use in acute simple and widely practicable treatment for acute
ischaemic stroke. ischaemic stroke could be shown reliably to produce even a
Methods The Chinese Acute Stroke Trial (CAST) was a large moderate improvement in outcome, the population benefit
randomised, placebo-controlled trial of the effects in could be substantial. Aspirin is effective in the treatment of
hospital of aspirin treatment (160 mg/day) star ted within acute myocardial infarction,4 and a systemic overview in
48 h of the onset of suspected acute ischaemic stroke and 1994 of all previous trials of long-term antiplatelet therapy
continued in hospital for up to 4 weeks. The primar y among patients with a history of previous myocardial
infarction, stroke, or transient ischaemic attack showed that
endpoints were death from any cause during the 4-week
about 40 serious vascular events (myocardial infarction,
treatment period and death or dependence at discharge, and
stroke, or vascular death) are avoided per 1000 patients
the analyses were by intention to treat. 21 106 patients
treated for a few years with aspirin.5 As a result, many
with acute ischaemic stroke were enrolled in 413 Chinese
patients admitted to hospital with strokes are now being
hospitals at a mean of 25 h after the onset of symptoms discharged on long-term low-dose aspirin (or other
(10 554 aspirin, 10 552 placebo). 87% had a CT scan before antiplatelet agents), not only in western countries,6 but also
randomisation. It was prospectively planned that the results in China7 and elsewhere.
would be analysed in parallel with those of the concurrent There is, however, little evidence on the balance of
International Stroke Trial (IST) of 20 000 patients with acute benefits and risks of antiplatelet therapy started during the
stroke from other countries. initial acute phase of ischaemic stroke.8,9 Consequently,
Findings There was a significant 14% (SD 7) propor tional there is much variation in routine clinical practice.6,7,10,11
The large, randomised, placebo-controlled Chinese Acute
reduction in mor tality during the scheduled treatment period
Stroke Trial (CAST), and the parallel International Stroke
(343 [3·3%] deaths among aspirin-allocated patients vs 398
Trial (IST)12 conducted in other countries, were designed
[3·9%] deaths among placebo-allocated patients; 2p=0·04).
to provide reliable evidence about the effects on early
There were significantly fewer recurrent ischaemic strokes
mortality and major morbidity of early aspirin treatment in
in the aspirin-allocated than in the placebo-allocated group a wide range of patients presenting with definite or
(167 [1·6%] vs 215 [2·1%]; 2p=0·01) but slightly more suspected ischaemic stroke. Both trials planned to enrol
haemorrhagic strokes (115 [1·1%] vs 93 [0·9%]; 2p>0·1). 20 000 patients, thereby yielding a total of 40 000.
For the combined in-hospital endpoint of death or non-fatal
stroke at 4 weeks, there was a 12% (6) propor tional risk Methods
reduction with aspirin (545 [5·3%] vs 614 [5·9%]; 2p=0·03),
Eligibility
an absolute difference of 6·8 (3·2) fewer cases per 1000. At
Patients admitted to the 413 participating hospitals in China were
discharge, 3153 (30·5%) aspirin-allocated patients and eligible for CAST if they were judged to be within 48 h of the
3266 (31·6%) placebo-allocated patients were dead or onset of symptoms of suspected acute ischaemic stroke, and had
dependent, corresponding to 11·4 (6·4) fewer per 1000 in no clear indications for, or contraindications to, aspirin.
favour of aspirin (2p=0·08). Contraindications were specified not by the protocol but by the
responsible physician, and were generally based on an expectation
Interpretation There are two major trials of aspirin in acute of either an increased risk of adverse effects (eg, because there was
ischaemic stroke. Taken together, CAST and the similarly a recent history of serious gastric bleeding or a known allergy to
large IST show reliably that aspirin star ted early in hospital aspirin), or little likelihood of any worthwhile benefit in hospital
produces a small but definite net benefit, with about 9 (SD (eg, because the patient had only a minor stroke, other major life-
threatening disease, or severe pre-existing disability). The
3) fewer deaths or non-fatal strokes per 1000 in the first few
fundamental criterion for entry was that the responsible physician
weeks (2p=0·001), and with 13 (5) fewer dead or was uncertain whether or not aspirin treatment was indicated for a
dependent per 1000 after some weeks or months of follow- particular patient. The protocol stated that the physician should
up (2p<0·01). discuss the study in an appropriate way with the patient or
relatives. No written consent was requested, since such a request
Lancet 1997; 349: 1641–49
may not be appropriate in an emergency setting.13
Recruitment began first in ten hospitals, as a pilot phase in
*Members of group and writing committee listed at end of paper which 600 patients were randomised. The aims of this phase were
Correspondence to: Dr Z heng-Ming Chen, Clinical Trial Ser vice to refine the trial practical procedures and to estimate the likely
Unit, Nuffield Depar tment of Clinical Medicine, Radcliffe Infirmar y, recruitment rates. Under the protocol, these patients would be
Oxford OX2 6HE, UK included in the total study sample.

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death or non-fatal stroke during the scheduled treatment period.


Other major clinical events during the scheduled treatment period,
such as transfused or fatal extracranial haemorrhage and
pulmonary embolus (clinical diagnosis), were also considered.
Non-fatal events were defined as those occurring among patients
who survived to the end of the scheduled treatment period. The
few patients who had more than one type of non-fatal event can
appear more than once in the tabulations. The main prespecified
subgroup analyses were of the effect of aspirin on death or non-
fatal stroke during the scheduled treatment period, subdivided by
hours of delay from onset of symptoms, previous CT scan, and
consciousness level at entry. Subgroup analyses according to
various other baseline charactersitics were also done.

Planned study size


Figure 1: Trial profile The planned sample size was 20 000 patients,17 which was based
on the assumption of 9% mortality in the placebo group during
the scheduled trial treatment period, with 15% of these deaths
CT scanning avoidable by aspirin. In a trial of 10 000 patients, even if the true
A CT scan before randomisation was mandatory only for patients effect of aspirin on early mortality were about 15% (which would
who were comatose. Other patients could be entered for lead to the prediction of about 380 aspirin-allocated vs 450
randomisation without a CT scan provided that the responsible placebo-allocated deaths), the effects of chance could well reduce
physican was reasonably certain that haemorrhagic stroke could be the observed difference to a not conventionally significant value
excluded. (eg, 400 vs 440 deaths). The aim of CAST, therefore, was to enter
at least 20 000 patients to reduce the risk of such a false-negative
Randomisation result. In addition, it was planned prospectively that this study
Randomisation was by prepacked, sequentially numbered trial would be analysed in parallel with the concurrent IST.
envelopes, each containing calendar-packed aspirin or placebo,
produced centrally. Within each hospital, random allocation to
aspirin or placebo was, unknown to the participating physicians, Number in allocated treatment group
balanced for every ten consecutive patients. Initially, 20 sealed Aspirin (n=10 554) Placebo (n=10 552)
envelopes were sent to each participating hospital, strung together
through punched holes in the order they were to be used. Sex
Male 6633 (63%) 6734 (64%)
Subsequent resupply depended on the speed of recruitment, Female 3921 (37%) 3818 (36%)
which was assessed by monitoring of the sequential return of entry
Age (years)
forms. To enter a patient into the trial, the responsible physician
<60 3361 (32%) 3369 (32%)
had simply to complete the one-page entry form attached to the 60–69 4214 (40%) 4202 (40%)
outside of the next trial envelope in the bundle. 肁70 2938 (28%) 2948 (28%)
Unknown 41 33

Trial treatment Time from onset (h)


0–3 453 (4%) 434 (4%)
After the entry form had been completed, the envelope was
4–6 823 (8%) 801 (8%)
opened, and the 4-week calendar pack of either 160 mg film- 7–12 1465 (14%) 1498 (14%)
coated aspirin tablets or matching placebo tablets was removed. 13–24 2888 (27%) 2859 (27%)
The doctor recorded the patient’s name on the drug pack, and 25–48 4906 (47%) 4932 (47%)
then gave the first trial tablet immediately, either crushed or Unknown 19 28
chewed, followed by one tablet each day for 4 weeks (or until Consciousness
earlier discharge or death). If the patient could not swallow the Drowsy/coma 1339 (13%) 1341 (13%)
tablets, nasogastric feeding tubes were used. All other decisions Fully alert 9201 (87%) 9198 (87%)
Unknown 14 13
about management of patients were at the discretion of the
responsible doctor, except that non-trial aspirin or other Atrial fibrillation
antiplatelet drugs were not allowed during the trial period unless Present 696 (7%) 715 (7%)
Absent 9811 (93%) 9790 (93%)
the doctor believed that the patient had developed some strong Unknown 47 47
indication for aspirin, such as acute myocardial infarction. Chinese
herbal products could be prescribed if considered indicated, even CT scan at entry
CT done, lesion visible 7843 (74%) 7859 (74%)
though some may affect platelets.14 CT done, lesion not visible 1379 (13%) 1385 (13%)
No CT 1264 (12%) 1257 (12%)
Discharge Unknown 68 51

At discharge (or death before discharge), a single-sided form was Systolic blood pressure (mm Hg)
completed and returned to the trial office in Beijing. This form <140 2599 (25%) 2596 (25%)
140–159 2861 (27%) 2838 (27%)
provided brief details of compliance with the study treatment, 160–179 2425 (23%) 2438 (23%)
possible side-effects, major clinical events, disability by the 180–199 1814 (17%) 1833 (17%)
modified Rankin disability scale,15,16 and, if the patient had died, 肁200 844 (8%) 835 (8%)
the likely primary cause of death. The protocol encouraged the Unknown 11 12
prescription of low-dose aspirin at discharge for the long-term Type of stroke*
prevention of recurrent stroke and other major vascular events. Total anterior 938 (9%) 954 (9%)
Partial anterior 5772 (55%) 5673 (54%)
Posterior circulation 698 (7%) 746 (7%)
Outcome measures and comparisons Lacunar infarct 3117 (29%) 3146 (30%)
The primary prespecified comparisons were of death from any Other unknown 29 33
cause during the scheduled treatment period (ie, in hospital within Discharge form available 10 335 (98%) 10 320 (98%)
4 weeks), and of death or dependence at discharge. Subsidiary *Based on Oxford Community Stroke Project (OCSP) classification.21
comparisons were of fatal or non-fatal recurrent stroke, and of
Table 1: Baseline characteristics by treatment group

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Number (%) of those with Absolute 2p were male, 72% were younger than 70 years, 26% were
discharge forms in benefit with within 12 h of symptom onset, 13% were drowsy or
allocated group aspirin per comatose, and 7% had atrial fibrillation. 87% had had a
1000 (SD)*
Aspirin Placebo CT scan before randomisation. Discharge forms were
(n=10 335) (n=10 320)
available by April, 1997, for 20 655 (97·9%) of the
Deaths randomised patients; forms were unavailable for similar
All deaths 343 (3·3%) 398 (3·9%) 5·4 (2·6) 0·04 numbers in the two treatment groups (figure 1). Of
Due to initial stroke 144 (1·4%) 175 (1·7%) 3·0 (1·7) 0·08 patients with discharge forms available, 94% (with 87%
Due to recurrent stroke (any type) 99 (1·0%) 108 (1·2%) 0·9 (1·4) >0·1
Due to other (or unknown) causes 100 (1·0%) 115 (1·1%) 1·5 (1·4) >0·1 scanned before randomisation) had at least one CT scan in
Recurrent stroke (fatal or not)
hospital, and the diagnosis of ischaemic stroke was
All 335 (3·2%) 351 (3·4%) 1·6 (2·5) >0·1 eventually confirmed in about 98% of the randomised
Ischaemic 167 (1·6%) 215 (2·1%) 4·7 (1·9) 0·01 patients. 302 patients (1·5%; 152 aspirin vs 150 placebo)
Haemorrhagic† 115 (1·1%) 93 (0·9%) ⫺2·1 (1·4) >0·1
Unknown 53 (0·5%) 43 (0·4%) ⫺1·0 (0·9) >0·1
were found to have been misdiagnosed at entry, including
174 (0·8%) with haemorrhagic strokes and 128 (0·6%)
Death or non-fatal stroke 545 (5·3%) 614 (5·9%) 6·8 (3·2) 0·03
with brain tumours or other diseases. All were included in
Pulmonary embolism the analyses for the intention-to-treat comparisons. The
All 12 (0·1%) 20 (0·2%) 0·8 (0·6) >0·1
Fatal 5 (0·1%) 10 (0·1%) 0·5 (0·4) >0·1 final diagnosis was not reported on the discharge form for
Non-fatal 7 (0·1%) 10 (0·1%) 0·3 (0·4) >0·1 152 patients (0·7% of those with forms; 73 vs 79). The
Transfused (or fatal) extracranial bleed average stay in hospital was about 4 weeks. 97% in each
All 86 (0·8%) 58 (0·6%) ⫺2·7 (1·2) 0·02 treatment group had completed their 4 weeks of trial
Fatal 39 (0·4%) 31 (0·3%) ⫺0·8 (0·8) >0·1
Non-fatal 47 (0·5%) 27 (0·3%) ⫺1·9 (0·8) 0·02
tablets or had continued to take the tablets throughout the
hospital stay if they died or were discharged during the first
*Negative numbers indicate more events occurred in aspirin than in placebo group.
†Includes cerebral haemorrhage or haemorrhagic transformation of original infarct. 4 weeks.
Table 2: Main clinical events in hospital during scheduled
(4-week) treatment period by allocated treatment Effects on mortality and recurrent stroke
There were 343 (3·3%) in-hospital deaths within 4 weeks
Statistical analyses among patients allocated aspirin compared with 398
The analyses compare all patients allocated aspirin with all those (3·9%) in the placebo group. The proportional reduction in
allocated placebo (intention to treat). Most involve simple the odds of death in the aspirin group (14% [SD 7]) is
comparisons18,19 of total numbers affected during the scheduled statistically significant (2p=0·04) and corresponds to an
treatment period. Absolute differences are given as benefits per absolute difference of 5·4 (SD 2·6) fewer deaths per 1000
1000 patients treated with aspirin, and proportional differences patients allocated aspirin for about 4 weeks
are given as odds ratios (or percentage reductions in the odds
(table 2). Of the deaths in hospital, about one third each
ratio), with SDs or CIs. Two-sided p values (2p) are given
throughout.
were attributed directly to the initial stroke, recurrent
Interim analyses of the primary endpoints were planned after stroke (which, by definition, includes ischaemic stroke,
5000, 10 000, and 15 000 patients had been recruited. In the light haemorrhagic stroke, or haemorrhagic transformation of
of these interim analyses and of any other evidence or advice they the original infarct), and other causes, most of which are
wished to seek, the data-monitoring committee would advise the likely to have been due indirectly to the initial stroke.There
chairman of the steering committee if there was at any time proof were slightly fewer deaths in each category of attributable
beyond reasonable doubt that treatment was either clearly causes of death among patients allocated aspirin than
indicated or clearly contraindicated for all, or for some, types of among those allocated placebo, but none of these
patient. Otherwise, the steering committee, collaborators, and differences was statistically significant (table 2).
administrative staff would not be informed of the interim results.
For the endpoint of fatal and non-fatal recurrent strokes
In September, 1996, the preliminary results from IST20 and
interim results on the first 14 000 patients in CAST were during the scheduled treatment period, there were 335
presented, and the collaborating doctors in CAST were informed (3·2%) among aspirin-allocated patients compared with
of the main results from both studies. Although the preliminary 351 (3·4%) in the placebo group. This difference, though
results were promising, the steering committee decided to not significant, combined a significant reduction of 4·7
continue randomisation in CAST to its scheduled end, with the (1·9) recurrent ischaemic strokes per 1000 (2p=0·01) with
principal entry criterion (as before) being the uncertainty of the
responsible physicians as to whether or not to use aspirin early in
the treatment of any particular patient presenting with suspected Number (%) of those with Absolute 2p
ischaemic stroke. discharge forms in benefit with
allocated group aspirin per
1000 (SD)*
Aspirin Placebo
Results (n=10 335) (n=10 320)
Characteristics of participants
Functional status of survivors†
21 106 patients with entry forms available by April, 1997, Total number of sur vivors 9915 ( 9853 (
were enrolled from 413 Chinese hospitals between Fully recovered 3840 (38·7%) 3716 (37·7%) ⫺10·1 (6·9) >0·1
November, 1993, and March, 1997 (figure 1). This large Independent, not fully recovered 3299 (33·3%) 3307 (33·6%) 2·9 (6·7) >0·1
Dependent 2776 (28·0%) 2830 (28·7%) 7·2 (6·4) >0·1
size ensured good balance between the aspirin and placebo
groups for the main prerandomisation prognostic features Dead 377 (3·6%) 436 (4·2%) 5·8 (2·7) 0·03

that were measured (table 1). The mean ages of the aspirin Dead or dependent 3153 (30·5%) 3266 (31·6%) 11·4 (6·4) 0·08
and placebo groups were 63·2 years (SD 10·4) and 63·1 *Negative numbers indicate more events occurred in aspirin than in placebo group.
years (10·3) years; the mean times from onset of symptoms †Information on disability at discharge not available for 74 sur vivors (43 aspirin, 31
placebo) who were excluded from this analysis.
were 24·9 h (14·1) and 25·1 h (14·2); and the mean Fully recovered=Rankin scale 0; independent, not fully recovered=Rankin scale 1–2;
systolic blood pressures were 156·8 mm Hg (27·9) and dependent=Rankin scale 肁3.
156·9 mm Hg (28·0). Of all patients randomised, 63% Table 3: Functional status at discharge

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Figure 2: Effects of early aspirin treatment in acute ischaemic stroke on death or non-fatal stroke during scheduled treatment period,
subdivided by prerandomisation features (CAST)
Odds ratio (black square, with area propor tional to amount of information contributed5) and 99% CI (horizontal line) plotted for various subgroups of
study population. A black square to the left of solid vertical line suggests a benefit, significant at 2p<0·01 only if whole 99% CI is to the left of solid
ver tical line. Overall result for all individuals entered (and 95% CI) is represented by a diamond. In each subdivision, any patients with missing
information were omitted.

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(table 3). Among patients who were independent at


discharge, 3840 (53·8% of those independent) aspirin-
allocated patients achieved full recovery compared with
3716 (52·9%) patients in the placebo group (2p>0·1).
Effects on other clinical events
Few cases of pulmonary embolism were recorded during
the scheduled treatment period, and there was no
significant difference between the treatment groups
(table 2). Aspirin was, however, associated with a small but
significant excess of 2·7 (SD 1·2) transfused or fatal
extracranial bleeds per 1000 during the scheduled
treatment period (86 [0·8%] vs 58 [0·6%]; 2p=0·02).
There is substantial overlap between deaths and major
events reported in hospital. To avoid double counting in
the assessment of any effect of aspirin, the analysis was
restricted to patients alive at the end of scheduled
treatment period. In this analysis, the numbers of non-fatal
pulmonary emboli reported in each group were similar
(seven vs ten), and the excess of non-fatal transfused
bleeds was 1·9 (SD 0·8) per 1000 (47 [0·5%] vs 27
[0·3%]; 2p=0·02). Information on non-fatal myocardial
infarction was not sought, but this event is relatively rare in
Chinese stroke patients.
Major subgroup analyses
Figure 2 shows the observed effects of aspirin on death or
non-fatal stroke during the scheduled treatment period
according to baseline features. There were no significant
differences in the effects of aspirin between the different
subgroups studied, including those prospectively identified
for study. For patients treated early or late after onset of
symptoms, the odds reductions for those randomised at
0–3 h, 4–6 h, 7–12 h, 13–24 h, and 25–48 h were: 36%
(SD 18), 15% (18), ⫺3% (16), 12% (11), and 13% (9),
respectively. For those randomised with or without a prior
CT scan the odds reductions were 11% (6) and 28% (17),
and for those with or without impaired consciousness at
entry the odds reductions were 15% (10) if drowsy and
11% (8) if alert. The analysis in figure 2 includes more
than 2600 patients who were drowsy or comatose when
enrolled; the prognosis in this large subgroup is poor (the
risk of death or non-fatal stroke during the treatment
period was 16·2% aspirin vs 18·5% placebo). The
Figure 3: CAST, IST, and MAST-I—overview of proportional prognosis for the 17 881 who were fully alert was much
effects of early aspirin treatment in acute ischaemic stroke better (3·7% deaths vs 4·1%). Thus, a similar proportional
Recurrent ischaemic stroke, haemorrhagic stroke, and death or non-fatal benefit in the poor-prognosis and good-prognosis
stroke=within scheduled treatment periods—ie, in hospital up to 4
weeks for CAST, 2 weeks for IST, and 10 days for MAST-I. subgroups would correspond to a greater absolute benefit
Dead or dependent=at end of follow-up—ie, at discharge for CAST, at 6 in those with a poor prognosis.
months for IST and MAST-I. Although aspirin appeared to have little effect in some
Symbols and conventions as in figure 2. MAST-I data exclude patients
allocated streptokinase. subgroups (such as those randomised at 7–12 h, or
younger patients), this is not good evidence that the real
a non-significant excess of 2·1 (1·4) haemorrhagic strokes effects in these subgroups differ from the effect observed
per 1000. For the combined endpoint of death or non-fatal overall, for, the effect of aspirin on death or non-fatal
stroke, there were 545 (5·3%) events in the aspirin group strokes in CAST as a whole is not highly significant and so
and 614 (5·9%) in the placebo group (2p=0·03). This 12% results in particular subgroups will not be reliable. Hence,
(6) proportional reduction corresponds to 6·8 (3·2) fewer the chief need is not to consider subgroups of CAST but to
cases per 1000 patients allocated aspirin. consider the CAST results together with the randomised
evidence from the other trials of aspirin.
Effects on disability at discharge
Survivors were classified at discharge as dependent, Discussion
independent but not fully recovered, or fully recovered. For Before CAST and IST12 (which also randomised about
the primary outcome of dead or dependent at discharge, 20 000 acute stroke patients), no reliable evidence was
there was a non-significant trend favouring those allocated available on the value of early antiplatelet therapy in acute
aspirin (3153 [30·5%] vs 3266 [31·6%]; 2p=0·08), ischaemic stroke, and there was particular concern about
corresponding to a reduction of 11·4 (6·4) per 1000 the potential risk of intracranial haemorrhage.6,11 These two

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were 11 (SD 6) fewer patients dead or dependent at


discharge per 1000 allocated aspirin, and in IST (which
assessed disability at 6 months) there was a similar benefit
of 13 per 1000.12 For these two trials together with the
small MAST-Italy trial, the benefit is 13 (SD 5) fewer dead
or dependent per 1000 (2p=0·007). This finding provides
substantial reassurance that the early use of aspirin does
not materially increase the prevalence of serious disability
among survivors.
Overall, the patients enrolled in CAST were mainly at
low risk, with in-hospital mortality only half that in IST,
even though the two studies had virtually identical entry
criteria. This difference in mortality is due partly to the
difference in the age distribution of the patients: in CAST,
72% were younger than 70, whereas in IST only 38% were
under age 70, reflecting demographic differences between
China and the countries where IST took place. It is also
due partly to the exclusion from CAST of some (though
not all) patients with severe stroke, perhaps because of
particular concerns among Chinese doctors about possible
haemorrhagic side-effects of aspirin or because of their
Figure 4: CAST, IST, and MAST-I—overview of absolute effects reluctance to use nasogastric tubes in patients unable to
of early aspirin treatment in acute ischaemic stroke on clinical swallow because of severe stroke. Another contributing
events during scheduled treatment periods (as in figure 3) factor may be differences in the clinical subtypes of stroke
Numbers on bars indicate actual number of cases. Error bars=1 SE for prevalent in Chinese and western populations. For
percentage. example, previous studies have suggested that stroke in
western populations is characterised by predominantly
large trials in about 40 000 randomised patients, together extracranial carotid-artery disease (with a substantial
with the non-fibrinolytic component of the smaller prevalence of cardioembolic stroke), whereas in China
MAST-Italy trial,8 show, however, that immediate intracranial small-vessel disease, which results in lacunar
treatment of acute ischaemic stroke with medium-dose infarction and haemorrhage, occurs more frequently.22,23
aspirin (160 or 300 mg daily) produces a modest, but Another difference is that in CAST there was widespread
definite (2p=0·001), net reduction in early death or non- use of other treatments (eg, 53% of patients received a
fatal stroke (figures 3 and 4: a systematic search identified calcium antagonist and 51% received various Chinese
no other aspirin trials9). In these trials, which included a herbal products), whereas virtually no other treatments
wide range of patients, aspirin caused about two (SD 1) were used commonly in IST. No substantial benefit for any
haemorrhagic strokes among every 1000 patients treated, of these additional treatments in acute stroke has been
but prevented about 11 (SD 3) other strokes or deaths in proven, however, and even if some do produce modest
hospital. Almost all the difference in fatal or non-fatal benefits they could not account for the large difference in
recurrent ischaemic or unknown stroke was confined to prognosis between the two trials.
ischaemic stroke (322 aspirin vs 457 control cases), a Despite the low overall risk of the CAST population, the
difference of 6·7 (SD 1·4) per 1000. For stroke with trial was large and included substantial numbers of patients
unknown aetiology, there were 175 aspirin and 181 control at high risk of early death (for example, more than 2600
cases. patients were drowsy or comatose at entry, of whom about
Overall, therefore, about nine (SD 3) deaths or non-fatal 16% died or suffered non-fatal stroke; figure 2). The results
strokes were avoided for every 1000 patients treated with of CAST and IST should therefore be applicable to stroke
aspirin for a few weeks from soon after the onset of acute patients at both low risk and high risk.
ischaemic stroke. Although CAST and IST each involved about 20 000
The background risk of haemorrhagic stroke was much patients, their results had to be combined, yielding
greater in CAST than in IST (nine per 1000 in CAST evidence from a total of 40 000, before the effects of
placebo group vs three per 1000 in those allocated no aspirin could be assessed reasonably reliably, since the
aspirin or heparin in IST), but the small absolute increase benefits are not as large in acute ischaemic stroke as in
in this risk associated with early use of aspirin was similar myocardial infarction.4 If this highly significant evidence of
in the two studies (excess two per 1000 in both trials). a small but real benefit does substantially alter medical
In many countries, though perhaps not in China, 1–2% practice, one important research implication is the need for
of acute stroke patients would also suffer a non-fatal more large-scale randomised trials in stroke medicine. As
myocardial infarction during the first few weeks in hospital. in the treatment of acute myocardial infarction, the
This risk is also likely to be reduced by aspirin,5 increasing expectation of large reductions in mortality and major
the net clinical benefit of nine per 1000 slightly, perhaps to morbidity from any single therapeutic agent is probably
about ten per 1000. This benefit from just a few weeks of unrealistic.24 Moderate treatment effects are more
aspirin given early in acute ischaemic stroke seems plausible, and may well be worthwhile if produced by
worthwhile, being about the same as the benefit from a widely practicable treatments. Reliable assessment of such
whole year of antiplatelet therapy in the long-term moderate effects may, however, require strict
secondary prevention of stroke.5 Moreover, there was no randomisation of several thousands, or even tens of
evidence of any adverse effect among survivors in thousands, of patients.
functional recovery after stroke. Overall in CAST, there Aspirin irreversibly inhibits platelet cyclo-oxygenase,

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thereby inhibiting platelet aggregability, and is the most (W H Ai); Feixi County People’s Hospital (S S Chen); Anqing Second
People’s Hospital (J C Yang); Shucheng County People’s Hospital
convenient and widely tested antiplatelet agent. There are (Y Y Song); Anqing Petrochemical General Hospital (J Hua); Qianshan
many different pathways involved in the aggregation of Country Hospital (L Z Ge); Xuancheng Prefecture Second People’s
platelets, and a combination of two effective antiplatelet Hospital (Z L Tang); Taihu County People’s Hospital (Z J Zhang).
agents working through different mechanisms might be Beijing: Beijing CCP School Hospital (Y C Xu); Jiuxianqiao Worker’s
Hospital (S S Wang); Capital Iron and Steel Hospital
more effective than a single agent. For example, (J Q Wang); Beijing Fengshen Hospital (X J Yang); Fengtai Great Wall
ticlopidine, which inhibits ADP-induced platelet Hospital (J Wang); Beijing 402 Hospital (L J Shi); Beijing Boai Hospital
aggregation, may add to the proven benefit of aspirin in (W J Zhou); China Aerospace Central Hospital (C Z Wang); Beijing
Aerospace 731 Hospital (X M Wang); Beijing Railway Hospital
patients at high risk of occlusive arterial disease,25 as may (J F Zhou); Beijing Haidian Hospital (Y H Li); PLA 304 Hospital
dipyridamole26 (although earlier trials had not suggested (X M Meng); PLA 309 Hospital (P X Liu); Fanshan District First Hospital
this5). However, particularly large trials will be needed to (J Z Li); Beijing Military District General Hospital (W M Yin); China Civil
Aviation Beijing Hospital (S Q Han); PLA General Hospital (G P Wang);
test whether the addition to aspirin of ticlopidine, Beijing Tiantan Hospital (J Long); Beijing Medical College Third Hospital
dipyridamole, or some newer antiplatelet agent (such as (S Q Zhao); PLA 292 Hospital (W L Wei, S P Kang); Chanping County
clopidogrel27) can produce significantly greater clinical Beijiao Hospital (Z C Li); Tong County Luhe Hospital (W L He); Beijing
Chuiyangliu Hospital (M Y Wu); Shunyi County Hospital (T H Dong);
benefit than aspirin alone.28 Beijing Shuili Hospital (J Fan); Changping County Hospital (K Y Song);
CAST and IST are directly relevant to the practicalities Guanganmen Hospital (G D Gao); Beijing Mentougou Hospital (X Liu);
of stroke management. CAST took place in a wide variety Beijing Air Force General Hospital (C S Shi); PLA Naval General Hospital
of specialist and non-specialist hospitals throughout China, (G F Liu). Fujian: Fujian Provincial Hospital (X Z Zhou); Lian Jian County
Hospital (J Q Chen). Gansu: Lanzhou Military District General Hospital
and IST in a similar range of hospitals in 36 different (J S Yang); Jinchun Nonferrous Metal Co. Hospital (P Q Wang).
countries. The identification of suitable patients did not Guangdong: Zhaoqin First People’s Hospital (K Z Lian). Guangxi: Guangxi
involve any material change in the normal patterns of Mingzhu Hospital (Y A Zhong); Liuzhou People’s Hospital (J Su).
Guizhou: Zunyi Medical College Hospital (W L Du); Guiyang Huaxi
investigation or diagnosis in either trial, and the trial Prefecture People’s Hospital (L P Zhao); Dujun Qiannanzhou People’s
treatments did not interfere with the use of most other Hospital (X J Liu). Hebei: Xingtai Third People’s Hospital (H C Ning);
treatments. Aspirin treatment does not necessitate careful Hebei Provincial People’s Hospital (X Z Wang); Qinghuangdao First
People’s Hospital (J Li); Baoding Second Hospital (Q S Du); Chengde
monitoring, so it can be used widely not only in developed Central Hospital (X L Zhao, R P Cheng); Shijiazhuang Baiqiuhen
countries but also in countries with limited medical International Peace Hospital (C Z Wang); Tangshan Third People’s Hospital
resources. For about 800 of the 40 000 patients in CAST (X C Wu); Baoding Second Central Hospital (Y S Li); Chengde Medical
College Hospital (Z J Dou); Chengde County Hospital (J Y Ji); Chengde
and IST, the initial diagnosis was wrong, and the patient Fengning County Hospital (G L Fu); Shiyan Dongfeng Automobile
had had a cerebral haemorrhage before randomisaton. Hospital (Q D Zhou); Wuhan Military Industry Hospital (J D Liu); Hubei
There was no indication in either trial, however, that these Finance and Trade Hospital (C Z Zhu); Jingsha Central Hospital
misdiagnosed patients were damaged by aspirin, so any (MH Zhang); Zigui County First People’s Hospital (F R Zeng);
Qinhuangdao Port Hospital (J Y Liu); Fengrun County Hospital
such hazard cannot be large. (J F Hao). Heilongjiang: Harbin Fourth Hospital (W Z Wang); Harbin
Hence, aspirin treatment should now be considered for Medical College First Hospital (Z B Wang); Harbin Medical College
almost all patients presenting with acute ischaemic stroke, Second Hospital (Y W Zheng); Mudanjiang First People’s Hospital
(Y J Zhao); Qiqihaer First Hospital (L H Zhao); Ningan People’s Hospital
provided that there are no strong contraindications and (L Men); Heilongjiang RedCross Hospital (S Y Yu); Harbin Second
that haemorrhagic stroke can be excluded with reasonable Hospital (Y Y Chi); Jiamushi Medical College First Teaching Hospital
probability, whether based on CT scan or not. If early (C H Jiang); Qiqihar Nenjiang Agriculture Administration Central Hospital
(S J Zhu); Archen People’s Hospital (K X Ju); Shanzhi People’s Hospital
aspirin treatment were to be given in hospital to one (A X Fu); Hailuan First People’s Hospital (Y Z Xiang); Qiqihar PLA 203
million new patients a year—a fraction of the worldwide Hospital (N G Li); Daqing Fourth Hospital (L Y Ma); Bin County People’s
total with acute ischaemic stroke1—about 10 000 early Hospital (G C Zhang); Mudanjiang Railway Hospital (Z J Lu); Harbin First
Hospital (X H Zhang); Qiqihar Second Hospital (Y X Song);Yichun
deaths, non-fatal strokes, or myocardial infarctions would Forestry Administration Central Hospital (G R Chen); Daqing Oil and
be avoided without any apparent increase in the prevalence Petroleum Administration Worker’s Hospital (Y T Dou); Harbin Railway
of disability among survivors. Furthermore, early aspirin Central Hospital (R H Han); Daxinganlin Forest Bureau Central Hospital
treatment in acute ischaemic stroke is likely to lead to more (S Y Li). Henan: Henan Medical College First Hospital (Z H Fan);
Zhengzhou Second People’s Hospital (L H Feng); Henan Hebi City
patients being sent home on long-term low-dose aspirin, Hospital (W P Zhao); Xingxian First People’s Hospital (W P Zhao); Henan
which is already of proven value,5 and this consequence will Lushan County Hospital (Y X Li); Henan Xi County Gongliao Hospital
reduce the mortality and major morbidity after stroke still (S L Zhang); Henan Traditional Medicine College First Teaching Hospital
(J L Wang); Xuchang Central Hospital (Z Z Hu); Zhengzhou PLA 460
further. Hospital (Z H Cheng); Zhengzhou Guomian Third Hospital (J Z Lu);
Zhengzhou Guomian Fourth Hospital (Q Y Tie); Luohe First People’s
CAST study organisation Hospital (Y F Wei); Qinyang People’s Hospital (M C Tian); Zhongyuan
Writing committee—Z M Chen, R Collins, L S Liu, H C Pan, R Peto, Oilfield Worker’s Central Hospital (Q Q Ma); Luoyang Second People’s
J X Xie. Hospital (H Q Tian); Henan Construction Worker’s Hospital (J X Dong);
Steering committee—Z M Chen (clinical coordinator), J M Hui, L S Liu Kaifeng County Central Hospital (S D Shi); Xinxiang Medical College
(chair), Z M Liu, R Peto, P Sandercock (IST liaison), W Q Wang, First Hospital (G M Li); Runan Country Worker’s Hospital (D H Peng);
Y X Wang, Z B Wang, J X Xie (coordinator), G X You, F L Zhang, Mengjin County People’s Hospital (Y L Lu); Jiaozuo People’s Hospital
H Q Zhang, Z Y Zhao. (Q F Pan); Xinxian Central Hospital (X E Chen); Changge People’s
Data monitoring committee—R Collins,Y P Guo, Z Qin. Hospital ( B C Li); Zhumadian Prefecture Hospital (W J Bo); Nanyan
Neurological advisory group—Y P Guo, Z Qin, X F Tang. County People’s Hospital (X F Li); Zhumadian Prefecture People’s
Coordinating centre—Beijing H Q Fang, X Y He, L S Liu, H L Ma, Hospital (H B Ma, F T Zhang); Zhoukou Prefecture People’s Hospital
G X Xiao, J X Xie, S Y Xu, A R Zhang, X E Zhang. (L L Tian); Luoyang Cotton Worker’s Hospital (Y Y Zhang); Kaifen First
Clinical Trial Service Unit, Oxford—J Boreham, Z M Chen, R Collins, People’s Hospital (M D Yin); Zhumadian People’s Hospital (S Q Wang);
J Godwin, H C Pan, R Peto. Xinxian Second People’s Hospital (P He); Sanmenxia People’s Hospital
Participating centres (by province)—Anhui: Chuzhou Third People’s (Z B Sun); Linbao People’s Hospital (T H Tu); Zhengzhou Seventh
Hospital (Z P Wang); Tonglin People’s Hospital (Y C Kang); Anhui People’s Hospital (Q Z Yang); Zhengzhou Fourth People’s Hospital
Provincial Hospital (B X Zhou); Bengbu Medical College Hospital (Z H Quan); Henan Provincial People’s Hospital (Y Li); Zhengzhou Great
(Y W Zhang); Anqing City Hospital (Z X Chen, J J Mo); Anhui Medical Wall Aluminum Worker’s Hospital (G B He); Zhengzhou Railway Central
College First Hospital (C Q Wang); Suzhou First People’s Hospital Hospital (S Y Ma); Xinyan Prefecture People’s Hospital (J Liu); Henan
(X M Wang); Hefei Second People’s Hospital (J X Liu); Huannan Dongshui Traditional Chinese Medicine College (Z S Li); Anyan People’s Hospital
Miner Hospital (F F Wang); Tongcheng County People’s Hospital (S Yao); Henan Medical College Second Hospital (Q Q Liu). Hubei: Jingsha
(Z G Xiang); Fuyang Third People’s Hospital (T X Wang); Caohu City First People’s Hospital (C S Zhao); Hubei Gezhouba Central Hospital
People’s Hospital (S Q Guo); Wangjiang County People’s Hospital (J Zhao); Xiangfan First People’s Hospital (J J Yang);Wuhan First People’s

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Hospital (J E Wang); );Wuhan Eleventh People’s Hospital (L Hu); Wuhan 401 Hospital (G W Zhong); Dongying People’s Hospital (Q Y Xue);
First Metallurgy Construction Company Hospital (H Z Cheng); Dongxi Huaifang Huaichai Hospital (S H Liu); Shangdong Zhuanye Co.Worker’s
District People’s Hospital (S B Xu); Jingmen First People’s Hospital Hospital (Q D Wang); Shandong Qianfushan Hospital (R H Zhu);Yuchen
(X D Liu); Hubei Li Yuan Hospital (S B Xu); Tianmen Second People’s People’s Hospital (W M Wang); Huaifang Hospital (N L Guo); Linqu
Hospital (Z R Tang); Guangshui First People’s Hospital (X C Peng); County People’s Hospital (X R Ma); Jiaxiang County People’s Hospital
Yingcheng People’s Hospital (X B Yin); Zigui County First People’s (D Q Zhuang); Qufu People’s Hospital (R F Du); Juye County People’s
Hospital (C M Zhao); Gongan County People’s Hospital (F D Chen); Hospital (G X Hao); Longri Kuangwuju Central Hospital (Z Z Fu);
Nanzhang County People’s Hospital (Q L Zhang); Enshi Autonomous Zhangqiu People’s Hospital (Q J Men); Shandong Medical Academy Keyun
Region People’s Hospital (Z S Han); Erzhou Second People’s Hospital Hospital (M H Liu); Shandong Huanhe Hospital (C S Shi); Wudi County
(Y S Wang); Laohekou First People’s Hospital (D C Xu); Xiangfan Central People’s Hospital (J C Li); Dezhou People’s Hospital (Z J Song, X G Ren);
Hospital (H X Peng); Gezhouba Three Gorges Hospital (P S Lei); Deye Jinan Third People’s Hospital (W R Ma); Wuaifan People’s Hospital
People’s Hospital (Z L Zheng); Suizhou First People’s Hospital (C Q Jiang); (F Z Meng); Zibo Central Hospital (K R Tang); Binzhou Prefecture Central
Wuhan 161 Central Hospital (Y Z Chen). Hunan: Yiyan Prefecture Hospital Hospital (X Z Yan); Taian First People’s Hospital (Y S Wang); Shandong
(J X Cao);Yiyan People’s Hospital (G F Cao); Chenzhou 331 Hospital Prison Administration Hospital (X M Du); Feicheng People’s Hospital
(L M Xie); Xiangtan Third People’s Hospital (L J Chen); Xianxian People’s (Y H Sun); Linyi PLA 146 Hospital (G F Zhou); Jinan Central Hospital
Hospital (C L Zhou); Hunan Medical College Second Hospital (X H Liu). Shanghai: Shanghai First People’s Hospital (F L Zhang);
(Y M Zhou); Cili County People Hospital (D Q Yan). Jiangsu: Xinghua Shanghai Hypertension Institute (X Y Wang); Shanghai Second Medical
City Hospital (C W Gao); Nianjing Railway Central Hospital (X G He); College Ninth Hospital (J X Jin); Ruijin Hospital (D M Hu); Xinhua
Xuzhou Fourth People’s Hospital (ZG Wei); Lianyungan First People’s Hospital (L H Yu); Shanghai Railway Central Hospital (J Y Sun); Huadong
Hospital (S Y Li);Yancheng First People’s Hospital (J G Gu); Zhangjiagang Hospital (Y S Jin); Songjiang County Central Hospital (Y F Zhang).
First People’s Hospital (L G Li); Suzhou Medical College Second Hospital Shanxi: Yunchen Prefecture Hospital (D Tong), Shanxi Medical College
(G F Shao); Xuzhou Medical College Hospital (M L Lian); Nanjing First Hospital (L H Wei); Shanxi Medical College Second Hospital
Military District General Hospital (Y Q Jin); Nanjing Medical College First (R Z Zhang); Xinzhou Prefecture People’s Hospital (H R Yang);Yangquan
Hospital (Q Tong,Y L Cheng); Nanjing Bayi Hospital (S Z Shao); Nanjing Mine Administration Hospital (Y S Wang); Meng County People’s Hospital
Gulou Hospital (X J Tang); Nanjing Navy 414 Hospital (H Wang); Hanmen (X M Cui). Sichuan: Chongqin Medical College First Hospital (P Man);
People’s Hospital (S R Zhu); Tongzhou People’s Hospital (C S Yao); Chengdu Third People’s Hospital (K L Zhang); Jinyan Central Hospital
Xuzhou First People’s Hospital (L S Zhou); Rugao People’s Hospital (X Y Wang); Chongqing Southwest Hospital (S Q Shao); Huaxi Medical
(X H Shen). Jiangxi: Nanchang First Hospital (M X Ou); Jiangxi Medical University First Hospital (M Liu, G G Yuan); Chengdu Traditional Chinese
College Second Hospital (Z L Fen); Gannan Medical College Hospital Medicine Hospital (J Liu); Chengdu 95 Hospital (M Ye); Chunbei Medical
(X K Liu). Jilin: Changchun Jilin University Hospital (Y R Shi); Changchun College Hospital (X Q Zheng); Shifang County Central Hospital
Diesel Engine Factory Hospital (Y H Feng); Jilin Medical College Hospital (J S Wang); Third Military Medical College Third Hospital (J Z Wang);
(X P Wang); Changchun Baiqiuhen Medical College Third Hospital Chengdu Fifth Yejin Construction Workers’ Hospital (M Chen); Chengdu
(Y Q Wu); Changchun Central Hospital (X Gao);Yanji People’s Hospital Stroke Prevention Hospital (C Yang); Pengan County People’s Hospital
(Y F Zhu); Dongbei Normal University Hospital (Y J Liu); Jihua Co. (Z X Pu); Deyang People’s Hospital (B Zhang); Deyang Second People’s
Worker’s Hospital (C N Zhu, P Y Sun); Jilin Prison Administration Central Hospital (B H Dang); Dazhou Prefecture People’s Hospital (P J Zhou);
Hospital (L J Wang); Gongzhulin City First Veteran Hospital Jintang County First People’s Hospital (C F Xu); Pangan General Hospital
(R Y Shi); Jilin University Hospital (Y X Gong); Changchun PLA 461 (S L Liu); Shuanliu County First People’s Hospital (G X Liu); Shuanliu
Hospital (R Q Gao); Jilin Medical College Cerebrovascular Institute County Second People’s Hospital (Y Wang); Mianyan Third People’s
(G Li); Changchun Second Hospital (X Peng); Changchun Baiqiuhen Hospital (G J Wang); Chongqing Emergency Medical Centre (S J Mao);
Medical College Second Hospital (Y Zhang); Jilin BaichengCentral Pujiang County People’s Hospital (J R Yang); Chongqing Second People’s
Hospital (Y Yu); Taonan Hospital (Y S Wang); Jilin Central Hospital Hospital (Z F Ma); Chinese Engineering Academy Hospital (B X Hu);
(W Q Li, SQ Wang); Dumen Hospital (Z J Li); Liaoyuan Central Hospital Wanxian Fourth People’s Hospital (HY Liao); Pengzhou People’s Hospital
(G Y Wang); Dunhua Hospital (S C Wen);Yanbian Medical College (Y Y Xiao); Guanghan Third People’s Hospital (Q R Yang); Lianshanzhou
Hospital (X J Han, G Wu);Yanji Hospital (C J Piao); Jilin Dianli Hospital First People’s Hospital (L Liu); Jianyan People’s Hospital (Z L Gong);
(M Fang); Jilin Huichun Hospital (R Z Luo); Jilin Baicheng Hospital Chinese Nuclear Industry 416 Hospital (H T Fu); Chengdu First People’s
(H R He); Siping Central Hospital (Y F Xue); Changchun China First Hospital (M L Chen); Chengdu Sixth People’s Hospital (C J Song);
Automobile Hospital (Y R Tong); Jilin Provincial Hospital (G L Zhang, Chengdu 107 Hospital (Y Q Peng); Sichuan Provincial People’s Hospital
R L Cao); Jilin Paper Industry Worker’s Hospital (L Y Shao);Yanbian (X R Zeng); Shuidianbu Wuju Central Worker’s Hospital (Y Y Huang);
Miaolin Cement Factory Hospital (S K LI); Helong People’s Hospital Mianyan People’s Hospital (Y Q Li); Xichong County People’s Hospital
(J Cui); Daan First Hospital (Z L Wang); Liaoyuan Mine Administration (R Z Feng); Zigong First People’s Hospital (M L Liu); Sichuan Medical
Workers’ Hospital (X S Wang); Taonan Neurological and Psychiatry Administration College Hospital (R X Xie); Sichuan Chemistry Industry
Hospital (S S Li); Jilin Hospital (S Liu); Shenyang Railway Bureau Dumen Worker’s Hospital (S Y Qin); Mianzhu County People’s Hospital
Hosptial (E H Li); Tumen Shiyan Paper Mill Hospital (C Y Li). Liaoning: (T L Cao); Jiajiang County People’s Hospital (C Z Xiao); Pi County
Shenyang Railway Bureau Hospital (S L Li); Dalian Thrombosis Institute People’s Hospital (S Liu); Neihui Third People’s Hospital (W Chen); Lezhi
(H Q Zhang); Anshan Cerebrovascular Centre (Y X Wang); Shenyang Tiexi County People’s Hospital (M L Liu). Tianjin: Tianjin Brain Disease
District Central Hospital (F Zhang); PLA 324 Hospital (Z C Tang); Hospital (S M Wang); Tianjin Hospital (Q Z Meng); Tianjin Red Cross
Shenyang Red Cross Hospital (B X Guo); Fushun Miner’s Hospital Hospital (Q L Jiang); Tianjin Xiqing Hospital (K Lin); Tianjin Nankai
(B H Chen); Benxi Central Hospital (B D Zhou); Liaoning Paramilitary Hospital (R J Zhang); Tianjin Third Hospital (P Wang); Tianjin Tanggu
Police General Hospital (A P Xu); Liaomei Co. Danai Hospital (F S Zhou); Hospital (J Y Zheng); Tianjin Institute of Geratology (Q F Meng); Tianjin
Dalian 523 Factory Worker’s Hospital (Y J Lin); Shenyang Fifth People’s Tianhe Hospital (J Y Li); Tianjin 272 Hospital (T Cai, Z F Liu); Tianjin
Hospital (G Q Yang); Angang Tiedong Hospital (J Y Li); Shenyang 242 Hongqiao Hospital (D M Fang). Xinjiang: Xinjiang Medical College First
Hospital (A H Wang); Angang Tiexi Hospital (J Sun,Y C Wang); Liaoning Hospital (D R Fang); Xinjiang Autonomous Region People’s Hospital
Shihua Co.Worker’s Hospital (W H Yu); Liaoyang Third People’s Hospital (Y H Tan);Wulumuqi Railway Central Hospital (D Y Liu);Wulumuqi
(M Chen); Railway Ministry 191 Hospital (CR Li); Chaoyang Second Friendship Hospital (T Q Zhou); Kalamayi Oil Administration General
People’s Hospital (X H Zhang); Dandong First People’s Hospital Hospital (L Wang) Yunnan: Kunming First People’s Hospital (J M Hui);
(S Q Zhou); Liaoyan Central Hospital (G X Cao); Fushun Central Hospital Yunnan Provincial Hospital (Z Z Zhu);Kunming Medical College Second
(T Xie); Shenyang Seventh People’s Hospital (Y Q Yang); Dalian Friendship Hospital (Y Li); Funming Medical College First Hospital (H W Jin);
Hospital (G Y Zhao); Shenyang Medical College Second Hospital Lincang Prefecture Hospital (X B Liu); Chengdu Military District
(X L Zhang); Angang Lishan Hospital (L J Zhao); Shenyang PLA 463 Kunming Hospital (J B Hou). Z hejiang: Shaoxin People’s Hospital
Hospital (W F Ma); Shenyan Dadong District Hospital (X R Tang); (Z Q Sa).
Shenyang Fourth People’s Hospital (B H Chen); Fushun Steel Hospital
(B J Han); Dalian Medical College First Hospital (X J Hong); Dalian PLA Acknowledgments
210 Hospital (Z R Yu); Dalian PLA 469 Hospital (F Tao); Chaoyang Thousands of patients and hundreds of doctors and nurses collaborated.
Central Hospital (G X Zhao); Shenyang 157 Hospital (L Li); Shenyang The study was funded through the Medical Research Council’s support for
Chinese and Western Medicine Thrombosis Centre (B R Zhao); Jingzhou the Clinical Trial Service Unit, and trial tablets were donated by Shandong
Central Hospital (C X Liu). Neimongol: Neimongol Women & Children Xinhua Pharmaceuticals and tested by Dr J McVittie, Oxford Department
Hospital (G Z Men); Neimongol Autonomous Region’s Hospital of Biochemistry. The study was conducted, analysed, and interpreted
(JC Zhou); Baotou Medical College Second Hospital (G F Zhao). Ningxia: independently of any companies.
Ningxia Medical College Hospital (S Q Yan) Shaanxi: Xian Fourth Military
Medical College Tangdu Hospital (Z Y Wu); Xian Fourth Hospital
(S Q Liu); Xian Central Hospital (H X Wu), Xian Medical College Second
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