Tenecteplase—What Have We Learned till Now? A Narrative Review

Tenecteplase (TNK), a genetically modified tissue plasminogen activator, has emerged as a promising alternative to alteplase (ALT) for intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). Our aim was to synthesize the current clinical evidence on TNK use in AIS patients, comparing efficacy, safety, and workflow benefits to ALT. A narrative review was conducted by searching PubMed and Scopus (January 2024–March 2025) for studies comparing TNK and ALT in AIS. A total of 35 eligible papers were included. Data were grouped by treatment scenario: IVT-only, bridging before endovascular therapy (EVT), and intra-arterial thrombolysis (IAT). The results showed that TNK is non-inferior—and in some analyses, superior—to ALT regarding functional outcomes, especially in large vessel occlusion. TNK facilitates shorter treatment delays due to its single-bolus administration. While some trials report higher rates of intracranial hemorrhage, overall safety and mortality are comparable. In conclusion, TNK appears to exert equivalent or superior efficacy and safety compared to ALT in multiple AIS scenarios. Its pharmacological and logistical advantages support its broader clinical adoption. Further trials are needed, especially for IAT, central retinal artery occlusion, and patients on dabigatran.