Association between brain imaging signs, early and late outcomes, and response to intravenous alteplase after acute @entity64 in the third International XXXX Trial (IST-3): secondary analysis of a randomised controlled trial.

@entity1 @entity64 @entity932 @entity548 @entity4 @entity1188 @entity194 @entity10334
BACKGROUND: Brain scans are essential to exclude @entity548 in @entity1 with suspected acute @entity64 before treatment with alteplase. However, @entity1 with early ischaemic signs could be at increased risk of @entity548 after alteplase treatment, and little information is available about whether pre-existing structural signs, which are common in older @entity1 , affect response to alteplase. We aimed to investigate the association between imaging signs on brain CT and outcomes after alteplase. METHODS: IST-3 was a multicentre, randomised controlled trial of intravenous alteplase (0  9 mg/kg) versus control within 6 h of acute @entity64 . The primary outcome was independence at 6 months (defined as an Oxford Handicap Scale [OHS] score of 0-2). 3035 @entity1 were enrolled to IST-3 and underwent prerandomisation brain CT. Experts who were unaware of the random allocation assessed scans for early signs of ischaemia (tissue hypoattenuation, @entity1188 extent, @entity4 , and hyperattenuated artery) and pre-existing signs ( @entity1188 , @entity10334 , and @entity194 ). In this prespecified analysis, we assessed interactions between these imaging signs, symptomatic @entity932 (a secondary outcome in IST-3) and independence at 6 months, and alteplase, adjusting for age, National Institutes of Health @entity64 Scale (NIHSS) score, and time to randomisation. This trial is registered at ISRCTN.com, number ISRCTN25765518. FINDINGS: 3017 @entity1 were assessed in this analysis, of whom 1507 were allocated alteplase and 1510 were assigned control. A reduction in independence was predicted by tissue hypoattenuation (odds ratio 0  66, 95% CI 0  55-0  81), large lesion (0  51, 0  38-0  68), @entity4 (0  59, 0  46-0  75), hyperattenuated artery (0  59, 0  47-0  75), @entity194 (0  74, 0  59-0  94), and @entity10334 (0  72, 0  59-0  87). Symptomatic @entity932 was predicted by @entity1188 (odds ratio 1  72, 95% CI 1  18-2  51), tissue hypoattenuation (1  54, 1  04-2  27), and hyperattenuated artery (1  54, 1  03-2  29). Some combinations of signs increased the absolute risk of symptomatic @entity932 (eg, both @entity1188 and hyperattenuated artery, excess with alteplase 13  8%, 95% CI 6  9-20  7; both signs absent, excess 3  2%, 1  4-5  1). However, no imaging findings-individually or combined-modified the effect of alteplase on independence or symptomatic @entity932 . INTERPRETATION: Some early ischaemic and pre-existing signs were associated with reduced independence at 6 months and increased symptomatic @entity932 . Although no interaction was noted between brain imaging signs and effects of alteplase on these outcomes, some combinations of signs increased some absolute risks. Pre-existing signs should be considered, in addition to early ischaemic signs, during the assessment of @entity1 with acute @entity64 . FUNDING: UK Medical Research Council, Health Foundation UK, @entity64 Association UK, Chest @entity64 Scotland, Scottish Funding Council SINAPSE Collaboration, and multiple governmental and philanthropic national funders.
