Abstract/Text: BACKGROUND: Computed tomography (CT) must be done before thrombolytic treatment of hyperacute ischaemic stroke, but the significance of early ischaemic change on CT is unclear. We tested a quantitative CT score, the Alberta Stroke Programme Early CT Score (ASPECTS).
METHODS: 203 consecutive patients with ischaemic stroke were treated with intravenous alteplase within 3 h of symptom onset in two North American teaching hospitals. All pretreatment CT scans were prospectively scored. The score divides the middle-cerebral-artery territory into ten regions of interest. Primary outcomes were symptomatic intracerebral haemorrhage and 3-month functional outcome. The sensitivity and specificity of ASPECTS for the primary outcomes were calculated. Logistic regression was used to test the association between the score on ASPECTS and the primary outcomes.
FINDINGS: Ischaemic changes on the baseline CT were seen in 117 (75%) of 156 treated patients with anterior-circulation ischaemia included in the analysis (23 had ischaemia in the posterior circulation and 24 were treated outside the protocol). Baseline ASPECTS value correlated inversely with the severity of stroke on the National Institutes of Health Stroke Scale (r=-0.56, p<0.001). Baseline ASPECTS value predicted functional outcome and symptomatic intracerebral haemorrhage (p<0.001, p=0.012, respectively). The sensitivity of ASPECTS for functional outcome was 0.78 and specificity 0.96; the values for symptomatic intracerebral haemorrhage were 0.90 and 0.62. Agreement between observers for ASPECTS, with knowledge of the affected hemisphere, was good (kappa statistic 0.71-0.89).
INTERPRETATION: This CT score is simple and reliable and identifies stroke patients unlikely to make an independent recovery despite thrombolytic treatment.

Abstract/Text: BACKGROUND: Only a few small trials have compared antithrombotic therapy (antiplatelet or anticoagulant agents) versus control in acute ischaemic stroke, and none has been large enough to provide reliable evidence on safety or efficacy.
METHODS: The International Stroke Trial (IST) was a large, randomised, open trial of up to 14 days of antithrombotic therapy started as soon as possible after stroke onset. The aim was to provide reliable evidence on the safety and efficacy of aspirin and of subcutaneous heparin. Half the patients were allocated unfractionated heparin (5000 or 12,500 IU bd [twice daily]), and half were allocated "avoid heparin"; and, in a factorial design, half were allocated aspirin 300 mg daily and half "avoid aspirin". The primary outcomes were death within 14 days and death or dependency at 6 months. 19,435 patients with suspected acute ischaemic stroke entering 467 hospitals in 36 countries were randomised within 48 hours of symptom onset.
RESULTS: Among heparin-allocated patients, there were non-significantly fewer deaths within 14 days (876 [9.0%] heparin vs 905 [9.3%] no heparin), corresponding to 3 (SD 4) fewer deaths per 1000 patients. At 6 months the percentage dead or dependent was identical in both groups (62.9%). Patients allocated to heparin had significantly fewer recurrent ischaemic strokes within 14 days (2.9% vs 3.8%) but this was offset by a similar-sized increase in haemorrhagic strokes (1.2% vs 0.4%), so the difference in death or non-fatal recurrent stroke (11.7% vs 12.0%) was not significant. Heparin was associated with a significant excess of 9 (SD 1) transfused or fatal extracranial bleeds per 1000. Compared with 5000 IU bd heparin, 12,500 IU bd heparin was associated with significantly more transfused or fatal extracranial bleeds, more haemorrhagic strokes, and more deaths or non-fatal strokes within 14 days (12.6% vs 10.8%). Among aspirin-allocated patients there were non-significantly fewer deaths within 14 days (872 [9.0%] vs 909 [9.4%]), corresponding to 4 (SD 4) fewer deaths per 1000 patients. At 6 months there was a non-significant trend towards a smaller percentage of the aspirin group being dead or dependent (62.2% vs 63.5%, 2p = 0.07), a difference of 13 (SD 7) per 1000; after adjustment for baseline prognosis the benefit from aspirin was significant (14 [SD 6] per 1000, 2p = 0.03). Aspirin-allocated patients had significantly fewer recurrent ischaemic strokes within 14 days (2.8% vs 3.9%) with no significant excess of haemorrhagic strokes (0.9% vs 0.8%), so the reduction in death or non-fatal recurrent stroke with aspirin (11.3% vs 12.4%) was significant. Aspirin was associated with a significant excess of 5 (SD 1) transfused or fatal extracranial bleeds per 1000; in the absence of heparin the excess was 2 (SD 1) and was not significant. There was no interaction between aspirin and heparin in the main outcomes.
INTERPRETATION: Neither heparin regimen offered any clinical advantage at 6 months. The results suggest that if heparin is given in routine clinical practice, the dose should not exceed 5000 IU subcutaneously twice daily. For aspirin, the IST suggests a small but worthwhile improvement at 6 months. Taking the IST together with the comparably large Chinese Acute Stroke Trial, aspirin produces a small but real reduction of about 10 deaths or recurrent strokes per 1000 during the first few weeks. Both trials suggest that aspirin should be started as soon as possible after the onset of ischaemic stroke; previous trials have already shown that continuation of low-dose aspirin gives protection in the longer term.