(Stroke. 2000;31:1240.)
© 2000 American Heart Association, Inc.
Original Contributions |
Indications for Early Aspirin Use in Acute Ischemic Stroke
A Combined Analysis of 40 000 Randomized Patients From the Chinese Acute Stroke Trial and the International Stroke Trial
From the Clinical Trial Service Unit and Epidemiological Studies Unit (Z.M.C., H.C.P., R.C., R.P.), Nuffield Department of Clinical Medicine, Radcliffe Infirmary, Oxford, UK; Department of Clinical Neurosciences (P.S., C.C., C.W.), Western General Hospital, Edinburgh, UK; and Hypertension Unit (L.S.L., J.X.X.), Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China.
Correspondence to Dr Z.M. Chen, CTSU, Radcliffe Infirmary, Oxford OX2 6HE, UK. E-mail zhengming.chen{at}ctsu.ox.ac.uk
Background and Purpose—Long-term daily aspirin is of benefit in the years after ischemic stroke, and 2 large randomized trials (the Chinese Acute Stroke Trial [CAST] and the International Stroke Trial [IST]), with 20 000 patients in each, have shown that starting daily aspirin promptly in patients with suspected acute ischemic stroke also reduces the immediate risk of further stroke or death in hospital and the overall risk of death or dependency. However, some uncertainty remains about the effects of early aspirin in particular categories of patient with acute stroke.
Methods—To assess the balance of benefits and risks of aspirin in particular categories of patient with acute stroke (eg, the elderly, those without a CT scan, or those with atrial fibrillation), a prospectively planned meta-analysis is presented of the data from 40 000 individual patients from both trials on events that occurred in the hospital during the scheduled treatment period (4 weeks in CAST, 2 weeks in IST), with 10 characteristics used to define 28 subgroups. This represents 99% of the worldwide evidence from randomized trials.
Results—There was a highly significant reduction of 7 per 1000
(SD 1) in recurrent ischemic stroke (320 [1.6%] aspirin
versus 457 [2.3%] control, 2P<0.000001) and a less
clearly significant reduction of 4 (SD 2) per 1000 in death without
further stroke (5.0% versus 5.4%, 2P=0.05). Against
these benefits, there was an increase of 2 (SD 1) per 1000 in
hemorrhagic stroke or hemorrhagic transformation of the original
infarct (1.0% versus 0.8%, 2P=0.07) and no apparent
effect on further stroke of unknown cause (0.9% versus 0.9%). In
total, therefore, there was a net decrease of 9 (SD 3) per 1000 in the
overall risk of further stroke or death in hospital (8.2% versus
9.1%, 2P=0.001). For the reduction of one third in
recurrent ischemic stroke, subgroup-specific analyses
found no significant heterogeneity of the proportional
benefit of aspirin (
218=20.9, NS), even
though the overall treatment effect
(21=24.8, 2P<0.000001) was
sufficiently large for such subgroup analyses to be
statistically informative. The absolute risk among control patients was
similar in all 28 subgroups, so the absolute reduction of 
7 per 1000
in recurrent ischemic stroke does not differ substantially with
respect to age, sex, level of consciousness, atrial fibrillation, CT
findings, blood pressure, stroke subtype, or concomitant heparin use.
There was no good evidence that the apparent decrease of 4 per 1000
in death without further stroke was reversed in any subgroup or that in
any subgroup the increase in hemorrhagic stroke was much larger than
the overall average of 2 per 1000. Finally, there was no significant
heterogeneity between the reductions in the composite
outcome of any further stroke or death
(218=16.5, NS). Among the 9000 patients
(22%) randomized without a prior CT scan, aspirin appeared to be of
net benefit with no unusual excess of hemorrhagic stroke; moreover,
even among the 800 (2%) who had inadvertently been
randomized after a hemorrhagic stroke, there was no evidence of net
hazard (further stroke or death, 63 aspirin versus 67 control).
Conclusions—Early aspirin is of benefit for a wide range of patients, and its prompt use should be routinely considered for all patients with suspected acute ischemic stroke, mainly to reduce the risk of early recurrence.
Key Words: aspirin • stroke, acute • stroke, ischemic • randomized controlled trials
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