Author: Lina Palaiodimou, MD
Affiliations: Second Department of Neurology, “Attikon” University Hospital, National and Kapodistrian University of Athens, Greece
Tenecteplase (TNK) is a third generation tissue plasminogen activator and is currently indicated for the thrombolytic treatment of acute myocardial infarction at a dose of 0.5mg/kg.1 Presenting higher fibrin specificity, no evidence of neurotoxicity or effect on blood-brain barrier and much higher resistance to tissue plasminogen activator inhibitor type 1 compared to alteplase, has emphasized the potential efficacy and safety of TNK in the treatment of acute ischemic stroke as well.2 Another important pharmacological property is the longer half-life of TNK, allowing for a single bolus injection and achieving a fast recanalization.3 The COVID-19 pandemic and the associated restrictions have highlighted even more the importance of this practical advantage of TNK over alteplase use, in the sense that it reduces the staff exposure to contagion.4
From theory to action, in 2021 and based on the results of the available randomized-controlled clinical trials (RCTs; ATTEST, Australian-TNK, and EXTEND-IA TNK trials),5,6 the European Stroke Organisation (ESO) presented the guidelines on intravenous thrombolysis for acute ischaemic stroke, recommending that in patients with large vessel occlusion (LVO), who are candidates for mechanical thrombectomy, and for whom intravenous thrombolysis is considered before thrombectomy, TNK at a dose 0.25mg/kg is suggested over alteplase.7 However, the quality of the evidence used for this recommendation is graded as low. Yet, TNK use could not be supported in unselected stroke patients by the ESO guidelines,7 based on the analysis of available RCT data (TNK-S2B and ATTEST trials).8,9
During the ESOC 2022, four RCTs regarding the use of TNK in acute ischemic stroke presented their results: AcT,10 NOR-TEST 2,11 TASTE-A,12 and TWIST13 trials. The AcT10 and the TASTE-A12 trials evaluated TNK at a dose of 0.25mg/kg for intravenous thrombolysis in eligible, yet unselected, patients within 4.5 hours of symptom onset, at different settings. AcT was a phase 3, pragmatic, prospective, randomized, open-label, controlled, blinded endpoint, non-inferiority trial (with a non-inferiority margin of 5%), that was conducted in primary and comprehensive stroke centers in Canada.10 According to the results of the AcT trial, 36.9% of the TNK-treated patients achieved mRS 0-1 at 3 months compared to 34.8% in the alteplase-treated group. Non inferiority of TNK versus alteplase was proven (unadjusted risk difference 2.1%; 95%CI: -2.6 to 6.9%), without any safety concerns raising.
TASTE-A was a phase 2, prospective, randomized, open-label, controlled, blinded endpoint, superiority trial, that was conducted in a single mobile stroke unit in Australia and randomized acute ischemic stroke patients eligible for intravenous thrombolysis, who were otherwise unselected.12 TNK-treated patients presented significantly smaller CT perfusion lesions (median of 12ml), as evaluated during hospital admission, versus alteplase-treated patients (median of 25ml). No difference was noted between the two arms regarding safety issues or 3-month mRS scores, including the mRS 0-1 (41.8% in the TNK group versus 40.8% in the alteplase group).
These results may potentially move forward the use of TNK at a dose of 0.25mg/kg for intravenous thrombolysis of acute stroke patients, also beyond selected patients with LVO and intended thrombectomy. More RCTs are currently ongoing and may strengthen the evidence to use TNK as intravenous thrombolytic treatment for acute ischemic stroke.
Conflict of interest statement
Dr. Palaiodimou reports no conflicts of interest.
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