Safety and Efficacy of Intravenous Alteplase for Acute Ischaemic Stroke in Patients With Prestroke Symptomaticity: An Analysis of the Virtual International Stroke Trials Archive

Abstract

Background: Randomised controlled trials (RCTs) for intravenous thrombolysis (IVT) in acute ischaemic stroke (AIS) historically excluded patients with pre-existing disability. This tradition echoes in clinical practice, despite evidence suggesting IVT improves chances of returning to prestroke functional status. We investigated the role of pre-existing symptomaticity by comparing IVT-treated versus IVT-withheld Modified Rankin Scale (mRS) 1 patients and mRS 0 versus mRS 1 IVT-treated patients.

Methods: The Virtual International Stroke Trials Archive (VISTA) has collated data from 38 AIS RCTs. Patients enrolled in trials whose investigative treatments reported no significant effect on outcomes or that were placebo-treated were eligible, yielding 3175 individual patient records. 2454 patients had prestroke mRS 0, and 721 had prestroke mRS 1. The negligible number of patients with prestroke mRS ≥ 2 prompted focus on prestroke mRS 1 patients. Propensity score and logistic regression were used to compare intracranial haemorrhage (ICH), neurological improvement, mortality, and functional outcome within 90 days.

Results: Of IVT-treated patients, mRS 1 subjects were female in higher proportion and had a more frequent history of stroke than mRS 0 subjects. Of mRS 1 patients, IVT-withheld subjects were older and had a more frequent history of stroke than IVT-treated subjects. No significant differences were found for National Institutes of Health Stroke Scale (NIHSS) severity and other baseline parameters. IVT-treated patients achieved significant neurological improvement more frequently than IVT-withheld patients (40.5% vs. 27.9%, p = 0.028; adjusted odds ratio (aOR) 1.53, 95% confidence interval (95% CI): 1.18–1.88), with no significant differences in mortality and favourable functional outcome. ICH was numerically higher among IVT-treated patients; however, this did not persist after matching and regression adjustment. Comparing IVT-treated mRS 0 and mRS 1 patients revealed no significant differences.

Conclusion: Our post hoc analysis of randomised data provides reassurance that IVT is safe and offers significant clinical benefit for AIS patients with pre-existing symptomaticity, as measured by the NIHSS. The lack of marked improvement on the mRS substantiates that the NIHSS is a key secondary outcome measure to capture recovery trajectories in studies concerned with reperfusion therapies.