Abstract 104: The Impact of Ischemic and Structural Brain Tissue Changes on Response to rt-PA: An Analysis of Imaging from 3035 Patients in The Third International Stroke Trial
Aim: Early infarct signs predict symptomatic intracranial haemorrhage (SICH) and poor outcome after stroke. Structural brain features increase with age. It is unclear if, or when, any of these imaging signs should influence decisions to use rt-PA. We assessed imaging, SICH, 6-month outcome and rt-PA effects in 3035 patients randomised in IST-3.
Methods: IST-3 was a randomised trial of iv rt-PA (0.9mg/kg) <6 hours of ischaemic stroke (ISRCTN25765518). All pre- and post-randomisation imaging was read centrally, masked, by international experts for early infarct signs (tissue hypodensity site/size, swelling, hyperdense artery) and structural brain changes (atrophy, leukoaraiosis, prior infarct) using validated scales. We tested associations between pre-treatment imaging, SICH, 6-month outcome and rt-PA effects, adjusted for time, NIHSS, age, with logistic regression.
Results: Of 3035 patients, (1515 rt-PA, 1520 control; baseline imaging CT 2848, 98%, MR 54, 2%), 1616 aged >80; 851 treated <3hr, 1177 3-4.5 and 1007 4.5-6hr; 40% had tissue hypodensity/swelling (ASPECTS <7 in 25%, 8-10 in 75%); 24% had hyperdense artery; 50% had leukoaraiosis, atrophy or prior infarct; 9% were totally normal. On adjusted analyses, no imaging feature alone modified rt-PA effects. SICH increased with prior infarct (OR 1.66, p=0.009), tissue hypodensity (1.51, p=0.04), hyperdense artery (1.51, p=0.04). 6-month independent survival decreased with hypodensity (0.66, p=0.000), swelling (0.59, p=0.000), hyperdense artery (0.59, p=0.000), leukoaraiosis (0.72, p=0.0008) and atrophy (0.74, p=0.01). On elimination modelling, prior infarct predicted 54% of SICH risk; swelling, hyperdense artery, leukoaraiosis each predicted 33% of poor outcome risk.
Conclusion: Amongst these 3035 patients, neither structural nor early ischaemic imaging features alone modify rt-PA effects, but can inform rt-PA treatment decisions where benefits are likely to be marginal by predicting risk of rt-PA-associated SICH and poor functional outcome. The results are also relevant to older as well as younger patients and to rt-PA given <3 as well as up to 6 hours after stroke.
- © 2012 by American Heart Association, Inc.