Optimising outcomes of intravenous thrombolysis in acute ischaemic stroke

Mahmood, Ammad (2024) Optimising outcomes of intravenous thrombolysis in acute ischaemic stroke. PhD thesis, University of Glasgow.

Abstract

Intravenous thrombolysis is an established treatment for selected patients with acute ischaemic stroke. Outcome after intravenous thrombolysis is dependent upon a number of modifiable and non-modifiable factors. This thesis explored three themes in addressing how outcome after intravenous thrombolysis can be optimised:

• The potential for tenecteplase to be a superior thrombolytic drug to alteplase

• Improved patient selection through CT perfusion studies identifying groups at risk of poor outcome or greater benefit

• The effect of patient heterogeneity on outcomes in trials of acute ischaemic stroke

Tenecteplase is emerging as an alternative thrombolytic to alteplase in acute ischaemic stroke. Tenecteplase was studied in a prospective imaging substudy of a large multi-centre randomised controlled trial of tenecteplase versus alteplase in patients conventionally eligible for intravenous thrombolysis. Tenecteplase was found, in patients treated with intravenous thrombolysis within 4.5 hours of ischaemic stroke onset, to have similar outcomes to alteplase in efficacy and safety in cases of large vessel occlusion; similar efficacy in those with mismatch of CT perfusion imaging; similar rates of early recanalisation; and similar degree of penumbral salvage. A meta-analysis of trials comparing tenecteplase and alteplase found superiority of tenecteplase in functional outcomes and similar safety outcomes.

Tenecteplase was also studied in retrospective analyses of a combined cohort from two previous randomised controlled trials comparing alteplase and tenecteplase. CT perfusion studies examined the effect of varying rates of progression in ischaemia after the onset of acute ischaemic stroke; and differences in blood brain barrier permeability and how this relates to haemorrhagic transformation. Ischaemic progression rate was found to be a predictor of follow up infarct volume and infarct growth and a non-significant trend towards lower follow up infarct volumes in fast progressors treated with tenecteplase compared to alteplase was found. Measures of blood brain barrier permeability were found to be predictive of haemorrhagic transformation and tenecteplase was associated with higher blood brain barrier permeability in cases of haemorrhagic transformation than alteplase.

Thirdly, the effect of heterogeneity in participants in clinical trials of stroke and its effect on outcomes was studied. Follow up infarct volume was found to mediate a larger proportion of the relation between clinical outcomes and recanalisation than previously suggested. Heterogeneity in ischaemic progression rate of participants in trials of intravenous thrombolysis and mechanical thrombectomy was explored to highlight the effect of heterogeneity on trial outcome.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: R Medicine > RC Internal medicine; R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Supervisor's Name: Muir, Professor Keith
• Date of Award: 2024
• Depositing User: Theses Team
• Unique ID: glathesis:2024-84808
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 14 Jan 2025 14:38
• Last Modified: 14 Jan 2025 14:39
• Thesis DOI: 10.5525/gla.thesis.84808
• URI: https://theses.gla.ac.uk/id/eprint/84808