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 (chi(2)(18)=20. 9, NS), even though the overall treatment effect (chi(2)(1)=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 approximately 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 approximately 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 approximately 2 per 1000. Finally, there was no significant heterogeneity between the reductions in the composite outcome of any further
stroke or death (chi(2)(18)=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: