Association of Fibrinolysis With Acute Ischemic Stroke Outcome in Patients Undergoing Thrombectomy: Modification by Additional Administration of tPA?

Background: For acute ischemic stroke due to intracranial large-vessel occlusion in the anterior circulation, guidelines recommend treatment with intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator and endovascular thrombectomy (EVT). We investigated whether plasma fibrinolysis biomarkers were associated with the treatment effect of EVT, with or without IVT with recombinant tissue plasminogen activator, and their potential implications for clinical and radiological outcomes. Methods: In this post hoc analysis of MR CLEAN-NO IV, we measured fibrinolytic biomarkers (tissue plasminogen activator, global clot lysis time, and D-dimer) before and 24 hours post reperfusion and assessed their associations with patients' clinical and radiological outcomes based on National Institutes of Health Stroke Scale score, modified Rankin Scale (mRS) score, post-EVT extended thrombolysis in cerebral infarction score, and final infarct size. To quantify these associations, we used linear and logistic regression. Results: Blood was collected from 214 of 536 included patients, who received IVT+EVT (N = 108) or EVT alone (N = 106). In the IVT+EVT group, D-dimer levels 24 hours after treatment were higher and clot lysis time lower than in the EVT group, indicating more fibrinolysis. Pearson correlation showed that high D-dimer levels before and 24 hours after EVT were correlated with unfavorable long-term functional outcomes (mRS at 90 days), and D-dimer levels 24 hours after EVT linked to large infarct size. High tissue plasminogen activator levels after IVT+EVT were correlated with successful reperfusion. However, regression analysis adjusted for confounders showed no associations between fibrinolytic biomarkers and clinical or radiological outcomes. Conclusion: None of the fibrinolysis biomarkers were independently associated with outcomes in adjusted regression analysis, failing to support their use as predictors for treatment decisions or therapeutic effectiveness. However, exploratory analyses suggested that higher tissue plasminogen activator levels after IVT+EVT correlated with successful reperfusion, whereas elevated D-dimer levels were linked to unfavorable outcomes and larger infarct size post-EVT. Larger studies are needed to clarify their role in stroke treatment with IVT and/or EVT. Clinical Trial Registration: This study is a substudy of the MR CLEAN-NO IV trial, which is registered at the ISRCTN registry (ISRCTN80619088, https://www.isrctn.com/ISRCTN80619088).