Table 3.
Fatal and non-fatal cerebral and non-cerebral events within 7 days of randomisation
| rt-PA (n=1515) | Control (n=1520*) |
Adjusted analysis† |
Absolute difference per 1000 (95% CI)‡ | ||||
|---|---|---|---|---|---|---|---|
| Odds ratio (95% CI) | p value | ||||||
| Cerebral events | |||||||
| Symptomatic swelling of original infarct§ | |||||||
| Non-fatal | 21 (1%) | 17 (1%) | 1·23 (0·64 to 2·35) | 0·539 | 3 (−5 to 11) | ||
| Fatal | 47 (3%) | 25 (2%) | 1·89 (1·14 to 3·14) | 0·013 | 15 (4 to 25) | ||
| Total | 68 (4%) | 42 (3%) | 1·66 (1·11 to 2·49) | 0·014 | 17 (4 to 31) | ||
| Symptomatic intracranial haemorrhage¶ | |||||||
| Non-fatal | 49 (3%) | 9 (1%) | 5·56 (2·72 to 11·4) | <0·0001 | 26 (17 to 36) | ||
| Fatal | 55 (4%) | 7 (<1%) | 8·12 (3·68 to 17·9) | <0·0001 | 32 (22 to 42) | ||
| Total | 104 (7%) | 16 (1%) | 6·94 (4·07 to 11·8) | <0·0001 | 58 (44 to 72) | ||
| Neurological deterioration not due to swelling or haemorrhage | |||||||
| Non-fatal | 107 (7%) | 79 (5%) | 1·37 (1·02 to 1·86) | 0·038 | 19 (2 to 36) | ||
| Fatal | 38 (3%) | 49 (3%) | 0·74 (0·48 to 1·14) | 0·167 | −7 (−19 to 5) | ||
| Total | 145 (10%) | 128 (8%) | 1·14 (0·88 to 1·46) | 0·320 | 11 (−9 to 32) | ||
| Recurrent ischaemic stroke | |||||||
| Non-fatal | 18 (1%) | 15 (1%) | 1·21 (0·61 to 2·42) | 0·583 | 2 (−5 to 9) | ||
| Fatal | 3 (0%) | 5 (<1%) | 0·61 (0·14 to 2·57) | 0·499 | −1 (−5 to 2) | ||
| Total | 21 (1%) | 20 (1%) | 1·06 (0·57 to 1·97) | 0·846 | 1 (−8 to 9) | ||
| Recurrent stroke of unknown type | |||||||
| Non-fatal | 1 (<1%) | 2 (<1%) | 0·50 (0·05 to 5·56) | 0·574 | −1 (−3 to 2) | ||
| Fatal | 2 (<1%) | 1 (<1%) | 1·98 (0·18 to 22·3) | 0·581 | 1 (−2 to 3) | ||
| Total | 3 (<1%) | 3 (<1%) | 0·98 (0·20 to 4·89) | 0·981 | 0 (−3 to 3) | ||
| Non-cerebral events‖ | |||||||
| Myocardial infarction | |||||||
| Non-fatal | 18 (1%) | 19 (1%) | 0·89 (0·46 to 1·71) | 0·717 | −1 (−8 to 7) | ||
| Fatal | 5 (<1%) | 4 (<1%) | 1·25 (0·33 to 4·68) | 0·738 | 1 (−3 to 5) | ||
| Total | 23 (2%) | 23 (2%) | 0·95 (0·53 to 1·71) | 0·859 | 0 (−9 to 9) | ||
| Extracranial bleed | |||||||
| Non-fatal | 14 (1%) | 1 (<1%) | 14·5 (1·90 to 110) | 0·010 | 9 (4 to 14) | ||
| Fatal | 2 (<1%) | 2 (<1%) | 0·99 (0·14 to 7·13) | 0·995 | 0 (−3 to 3) | ||
| Total | 16 (1%) | 3 (<1%) | 5·46 (1·59 to 18·8) | 0·007 | 9 (3 to 14) | ||
| Allergic reaction | |||||||
| Non-fatal | 12 (1%) | 0 (0%) | ‥ | ‥ | 8 (3 to 12) | ||
| Fatal | 0 (0%) | 0 (0%) | ‥ | ‥ | 0 (0 to 0) | ||
| Total | 12 (1%) | 0 (0%) | ‥ | ‥ | 8 (3 to 12) | ||
| Total deaths from cerebral causes within 7 days | 145 (10%) | 87 (6%) | 1·76 (1·32 to 2·34) | 0·0001 | 38 (20 to 57) | ||
| Total deaths from non-cerebral causes within 7 days** | 18 (1%) | 20 (1%) | 0·89 (0·47 to 1·69) | 0·717 | −1 (−9 to 7) | ||
| Total deaths within 7 days | 163 (11%) | 107 (7%) | 1·60 (1·22 to 2·08) | 0·001 | 37 (17 to 57) | ||
Data are number (%) unless otherwise stated. rt-PA=recombinant tissue plasminogen activator.
One patient in the control group was missing a 7-day form but did return a 6-month form, so was known to be alive at 7 days. This case has been omitted from the analysis.
Odds ratio and p value calculated from logistic regression after adjusting for age (linear), National Institutes of Health Stroke Scale (linear), time (linear), and presence or absence of visible acute ischaemic change on baseline scan. When no events occurred in one treatment group the logistic model was not applied.
Absolute difference was calculated as rt-PA–control, so a positive number indicates this outcome was more frequent in the treatment group.
Symptomatic swelling of the original infarct was defined as significant neurological deterioration accompanied by evidence of significant brain swelling as determined by the independent masked expert assessment of the scan defined as: shift of the midline away from the side of the ventricle or effacement of the basal cisterns or uncal herniation on a postrandomisation scan (or autopsy if not rescanned before death). The presence of some degree of haemorrhagic transformation was permitted, provided it was not identified by the expert CT reader to be a major contributor to the mass effect.
Symptomatic intracranial haemorrhage was defined as significant neurological deterioration accompanied by clear evidence of significant intracranial haemorrhage on the postrandomisation scan (or autopsy if not rescanned and death occurs after 7 days). Significant haemorrhage was present on any postrandomisation scan if the expert reader both noted the presence of significant haemorrhagic transformation of the infarct or parenchymal haematoma and indicated that haemorrhage was a major component of the lesion (or was remote from the lesion and likely to have contributed significantly to the burden of brain damage). This event included clinical events described as a recurrent stroke within 7 days, in which the recurrent stroke was confirmed to be caused by an intracranial haemorrhage.
Non-fatal cerebral events are exclusive. However, non-fatal non-cerebral events are not exclusive. A given patient could have one or more non-fatal non-cerebral events and a non-fatal cerebral event.
The deaths in the fatal rows are exclusive (a patient can only contribute to one of the fatal rows). Total deaths from non-cerebral causes include deaths not attributed to myocardial infarction, extracranial bleed, or allergic reaction.