Subtypes of ischemic stroke : analysis of revascularization therapy, stroke etiology, and the role of blood pressure

Background: Treatment with intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT) improve outcomes for patients with acute ischemic stroke. The efficacy and safety of IVT and EVT may differ based on specific patient subgroups. Where, and in essence how, the blood clot was formed may affect treatment outcomes. Similarly, a patient’s blood pressure (BP) after a treatment may alter the treatment’s effect. This doctoral thesis aims to investigate how stroke etiology and different blood pressure parameters may affect patients with acute ischemic stroke treated with IVT or EVT.

Methods: All projects performed retrospective analyses on acute ischemic stroke patients in prospectively collected databases. Project 1-4 used the Safe implementation of treatment in stroke (SITS) international database. Project 5 registered all patients treated with EVT at the Karolinska University hospital during 2018-02-12 – 2020-02-11. Projects 1 and 3 investigated stroke etiologies, with project 1 investigating IVT treatment for patients with a lacunar stroke while project 3 compared EVT treatment for patients with large artery atherosclerosis and cardiac embolism. Projects 2, 4, and 5 investigated the effect of mean systolic BP (SBP), SBP change, and SBP course during the first 24 hours after EVT treatment, respectively. Primary outcomes were functional independence defined as a modified Rankin scale (mRS) score of 0-2 at 3-month follow-up, and successful reperfusion defined as a modified treatment in cerebral infarction score of 2b-3. Secondary outcomes included death by 3-month follow-up and symptomatic intracerebral hemorrhage (SICH). Multivariate regression analyses, including linear, logistic, and Poisson models, were used in the projects where applicable to adjust for potential confounding effects, in addition to propensity score matching in project 1. Projects 1 and 3 included unadjusted aggregate data meta-analyses of current literature.

Results: Project 1 found that IVT treatment led to better outcomes for LS patients when compared to non-IVT treated LS patients and non-LS IVT treated patients, respectively, which was also confirmed in an unadjusted meta-analysis of 13 studies. Project 3 found that after adjusting for known confounders, LAA patients had worse outcomes that patients with CE. However, the unadjusted meta-analysis of 25 studies did not find any difference. Project 2 found that higher mean SBP after EVT was associated with lower chances of functional independence for patients with successful reperfusion, and a higher risk of SICH regardless of reperfusion grade. Projects 4 and 5 found that an increase in SBP or a deviation from a linear decreasing SBP course after EVT treatment were associated with worse outcomes, respectively.

Conclusions: The projects in this thesis highlight the associations of stroke etiology and BP with outcomes after reperfusion therapy in acute ischemic stroke patients, suggesting that lacunar stroke patients should not be denied IVT treatment if otherwise eligible, that stroke etiology may affect EVT outcomes, and that generally higher SBP values over the first 24 hours after EVT treatment were associated with worse outcomes.

List of scientific papers

I. Matusevičius M, Paciaroni M, Caso V, Bottai M, Khurana D, de Bastos M, Martins S C O, Krespi Y, Cooray C, Toni D, Ahmed N. Outcome after intravenous thrombolysis in patients with acute lacunar stroke: An observational study based on SITS international registry and a meta-analysis. International journal of Stroke. 2019;14:878-86.
https://doi.org/10.1177/1747493019840947

II. Matusevičius M, Cooray C, Bottai M, Mazya M, Tsivgoulis G, Paiva Nunes A, Moreira T, Ollikainen J, Tassi R, Strbian D, Toni D, Holmin S, Ahmed N. Blood Pressure After Endovascular Thrombectomy: Modeling for Outcomes Based on Recanalization Status. Stroke. 2020;51:519-25.
https://doi.org/10.1161/STROKEAHA.119.026914

III. Matusevičius M, Cooray C, Rand V-M, Paiva Nunes A, Moreira T, Tassi R, Egido J A, Ollikainen J, Bigliardi G, Holmin S, Ahmed N. Stroke etiology and outcomes after endovascular thrombectomy: Results from the SITS registry and a meta-analysis. [Accepted]
https://doi.org/10.5853/jos.2021.00850

IV. Anadani M, Matusevičius M, Tsivgoulis G, Peeters A, Paiva Nunes A, Mancuso M, Roffe C, de Havenon A, Ahmed N. Magnitude of blood pressure change and clinical outcomes after thrombectomy in stroke caused by large artery occlusion. European journal of neurology. 2021;28(6):1922-30.
https://doi.org/10.1111/ene.14807

V. Matusevičius M, Cooray C, Holmin S, Bottai M, Ahmed N. Association between systolic blood pressure course and outcomes after stroke thrombectomy. [Submitted]