SGEM#377: You Don’t Have to “AcT” that Way – TNK for Acute Ischemic Stroke?

Date: September 20th, 2022 Reference: Menon et al. Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial. The Lancet 2022 Guest Skeptic: Professor Daniel Fatovich is an emergency physician and clinical researcher based at Royal Perth Hospital, Western Australia. He is Head of the Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research; Professor of Emergency Medicine, University of Western Australia; and Director of Research for East Metropolitan Health Service. Case: A 74-year-old man arrives from home by private vehicle complaining of right-sided weakness and dysarthria beginning two hours prior to arrival. Advance neuroimaging demonstrates no bleed and no large vessel occlusion. His NIHSS score is calculated to be 10 and he has no absolute contra-indications for systemic thrombolysis. Background: A lot has happened since you were on the SGEM last time discussing stroke (SGEM#325). This includes the CADTH report on thrombolysis by Alteplase for acute ischemic stroke in less than 4.5 hours with a letter to the editor from some neurologists representing CSC expressing their serious concerns about the report. Neurologist Dr. Ravi Garg was on an SGEM Xtra discussing his publication analysing the 1995 NINDS study. He showed the study had a high risk of selection bias. Dr. Garg concluded that the baseline imbalances observed in the NINDS study were more likely due to randomization errors than random chance. His advice was treatment decisions and guideline recommendations based on the original treatment effect reported in the NINDS tPA study should be done cautiously. We also had stroke neurologist Dr. Jeff Saver on an SGEM Xtra discussing his SRMA using the fragility index. He holds a much different interpretation of the stroke literature than Dr. Garg. The conclusion to Dr. Saver’s publication was that intravenous alteplase given within three hours of symptom onset for acute ischemic stroke is one of the most robustly proven therapies in medicine. Besides the disagreement about the strength of the evidence for tPA, there are challenges with administering this medication. It involves giving an infusion of 0.9mg/kg IV to a maximum dose of 90mg. The infusion starts with 10% of the total dose given as a bolus administered in one minute. The remaining amount is infused over 60 minutes.  Tenecteplase (TNK) is a genetically modified variant of alteplase with greater fibrin specificity (15-fold higher) and longer plasma half-life (22 min vs 3.5 min). Because of its ease of use as a single bolus and more favourable benefit-to-risk profile, it is preferred over alteplase as the fibrinolytic agent of choice for acute myocardial infarction. Clinical Question: Is tenecteplase non-inferior to alteplase in treating acute ischemic stroke? Reference: Menon et al. Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial. The Lancet 2022 Population: Adult patients aged 18 years and older with ischemic stroke who met eligibility criteria for alteplase (ischemic stroke causing disabling neurologic deficit, within 4.5 hours of onset). Patients eligible for endovascular thrombectomy in addition to intravenous thrombolysis were eligible for enrolment. Exclusions: Standard contraindications to IV thrombolysis Intervention: Tenecteplase (0.25 mg/kg) bolus Comparison: Alteplase (0.09 mg/kg bolus + 60 min infusion total 0.9 mg/kg to maximum of 90mg) Outcome: Primary Outcome: Proportion mRS 0-1 at 90 days, up to 120 days Secondary Outcomes: mRS 0-2 at 90-120 days; 90-120 day EQ-VAS & EQ-5D-5L, door to needle time, proportion given endovascular therapy,