Background Alteplase improves functional outcomes of patients with acute ischaemic stroke, but its effects on symptomatic infarct swelling, an adverse complication of stroke and the influence of CT hyperdense artery sign (HAS) are unclear. This substudy of the Third International Stroke Trial aimed to investigate the association between HAS and symptomatic infarct swelling and effect of intravenous alteplase on this association. Methods We included stroke patients whose prerandomisation scan was non-contrast CT. Raters, masked to clinical information, assessed baseline (prerandomisation) and follow-up (24–48 hours postrandomisation) CT scans for HAS, defined as an intracranial artery appearing denser than contralateral arteries. Symptomatic infarct swelling was defined as clinically significant neurological deterioration ≤7 days after stroke with radiological evidence of midline shift, effacement of basal cisterns or uncal herniation. Results Among 2961 patients, HAS presence at baseline was associated with higher risk of symptomatic infarct swelling (OR 2.21; 95% CI 1.42 to 3.44). Alteplase increased the risk of swelling (OR 1.69; 95% CI 1.11 to 2.57), with no difference between patients with and those without baseline HAS (p=0.49). In patients with baseline HAS, alteplase reduced the proportion with HAS at follow-up (OR 0.67; 95% CI 0.50 to 0.91), where HAS disappearance was associated with reduced risk of swelling (OR 0.25, 95% CI 0.14 to 0.47). Conclusion Although alteplase was associated with increased risk of symptomatic infarct swelling in patients with or without baseline HAS, it was also associated with accelerated clearance of HAS, which in return reduced swelling, providing further mechanistic insights to underpin the benefits of alteplase. The IST-3 data are deposited at , available on application to the study investigators.

中文翻译：

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高密度动脉征、症状性梗死肿胀及阿替普酶在急性缺血性卒中中的作用

背景 阿替普酶可改善急性缺血性卒中患者的功能预后，但其对症状性梗死肿胀、卒中不良并发症和 CT 高密度动脉征 (HAS) 的影响尚不清楚。第三次国际卒中试验的这项子研究旨在调查 HAS 与症状性梗塞肿胀之间的关联以及静脉阿替普酶对这种关联的影响。方法 我们纳入了随机化前扫描为非增强 CT 的中风患者。评估者对临床信息不知情，评估基线（随机化前）和随访（随机化后 24-48 小时）CT 扫描的 HAS，定义为颅内动脉比对侧动脉密度更大。有症状的梗塞肿胀被定义为中风后≤7天的临床显着神经功能恶化，放射学证据显示中线移位、基底池消失或钩索突出。结果 在 2961 名患者中，基线时存在 HAS 与更高的症状性梗死肿胀风险相关（OR 2.21；95% CI 1.42 至 3.44）。阿替普酶增加了肿胀的风险（OR 1.69；95% CI 1.11 至 2.57），基线 HAS 患者与无基线 HAS 患者之间没有差异（p=0.49）。在基线 HAS 患者中，阿替普酶降低了随访时 HAS 的比例（OR 0.67；95% CI 0.50 至 0.91），其中 HAS 消失与肿胀风险降低相关（OR 0.25，95% CI 0.14 至 0.47）。结论 尽管阿替普酶与基线 HAS 患者或非基线 HAS 患者出现症状性梗死肿胀的风险增加相关，但它也与加速清除 HAS 相关，这反过来减少肿胀，为支持阿替普酶的益处提供进一步的机制见解。IST-3 数据存放在，可根据研究人员的申请获得。