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Review
. 2023 May;22(5):418-429.
doi: 10.1016/S1474-4422(22)00519-1. Epub 2023 Mar 9.

Thrombolysis for acute ischaemic stroke: current status and future perspectives

Affiliations
Review

Thrombolysis for acute ischaemic stroke: current status and future perspectives

Georgios Tsivgoulis et al. Lancet Neurol. 2023 May.

Abstract

Alteplase is currently the only approved thrombolytic agent for treatment of acute ischaemic stroke, but interest is burgeoning in the development of new thrombolytic agents for systemic reperfusion with an improved safety profile, increased efficacy, and convenient delivery. Tenecteplase has emerged as a potential alternative thrombolytic agent that might be preferred over alteplase because of its ease of administration and reported efficacy in patients with large vessel occlusion. Ongoing research efforts are also looking at potential improvements in recanalisation with the use of adjunct therapies to intravenous thrombolysis. New treatment strategies are also emerging that aim to reduce the risk of vessel reocclusion after intravenous thrombolysis administration. Other research endeavors are looking at the use of intra-arterial thrombolysis after mechanical thrombectomy to induce tissue reperfusion. The growing implementation of mobile stroke units and advanced neuroimaging could boost the number of patients who can receive intravenous thrombolysis by shortening onset-to-treatment times and identifying patients with salvageable penumbra. Continued improvements in this area will be essential to facilitate the ongoing research endeavors and to improve delivery of new interventions.

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Conflict of interest statement

Declaration of interests GTs serves on the adjudication committee of the BI 1123-0040 trial (a phase 3, multicentre, prospective, randomised, open-label, blinded endpoint [PROBE], active-controlled parallel group trial to assess the efficacy and safety of Tenecteplase vs alteplase in Chinese patients with acute ischaemic stroke within 4·5 h after stroke onset). AHK serves as an investigator for the Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke (AcT), Tenecteplase in Stroke Patients Between 4·5 and 24 Hours (TIMELESS), and A Randomized Controlled Trial of TNK-tPA Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion (TEMPO-2). TNN reports research support from Medtronic and the Society of Vascular and Interventional Neurology (unrelated). UF reports research support from the Swiss National Science Foundation and the Swiss Heart Foundation; research grants from Medtronic (BEYOND SWIFT, SWIFT DIRECT) and from Stryker, Rapid medical, Penumbra, and Phenox (DISTAL); consultancies for Medtronic, Stryker, and CSL Behring (fees paid to institution); participation in an advisory board for Alexion/Portola and Boehringer Ingelheim (fees paid to institution); is a member of a clinical event committee of the COATING study (Phenox) and the data and safety monitoring committee of the TITAN, LATE_MT and IN EXTREMIS trials; and is Vice President of the Swiss Neurological Society. AB has received speakers fees from Boehringer Ingelheim. GTu is a member of the executive committee of the Tenecteplase Treatment in Ischemic Stroke (TETRIS) registry, which is financially supported by Boehringer Ingelheim. PK reports a grant from Cerenovus (ENDOLOW trial testing EVT for ischaemic stroke with low NIHSS); personal fees from Bayer (national leader of Bayer-PACIFIC trial testing Factor XIa inhibition for stroke prevention), Lumosa (data safety monitoring board and scientific advisory board for development of novel thrombolytic), Basking Biosciences (scientific advisory board for development of novel thrombolytic), and Diamedica (scientific advisory board for development of novel cytoprotective agent); and royalties from UpToDate for an online publication, outside the scope of the current work; and funds to their department from Genentech over 48 months ago for effort as lead principal investigator of the PRISMS trial, which tested alteplase for mild ischaemic stroke.

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