Advances in intravenous thrombolysis with tenecteplase in the ultra-time window

TL;DR

This paper reviews how tenecteplase improves stroke treatment beyond the traditional 4.5-hour window when used with imaging to identify suitable patients.

Contribution

The paper systematically reviews recent clinical findings on tenecteplase's effectiveness in ultra-time window thrombolysis.

Findings

Tenecteplase shows noninferiority to alteplase within 4.5 hours and better reperfusion in large vessel occlusions.

Ultra-time window studies show tenecteplase improves outcomes for patients with ischemic penumbra between 4.5–24 hours.

Some studies suggest reperfusion benefits without improved prognosis, highlighting the need for combined therapies and imaging.

Abstract

Worldwide, stroke has become a significant public health concern, with ischemic strokes accounting for over 70% among all stroke types. Intravenous thrombolysis (IVT), as a traditional treatment method, is limited by a narrow 4.5-h time window, which restricts its application. The conception of a “tissue window” for imaging evaluation has prompted a change in treatment strategy in recent years, and the time window has been gradually expanded to 24 h. Tenecteplase (TNK), a third-generation thrombolytic medication with a long half-life, good fibrin specificity, and minimal risk of bleeding, has garnered significant research interest in ultra-time window thrombolysis. TNK is noninferior to alteplase (rt-PA) at 4.5 h and has a superior reperfusion rate in patients with large vessel occlusion in the anterior circulation, according to several phase III randomized controlled studies (e.g., AcT, TRACE-2, ORIGINAL). Ultra-time window studies (e.g., TRACE-3 and TIMELESS) have demonstrated that TNK has a positive safety profile and substantially enhances functional outcomes in patients who possess an ischemic penumbra detected by imaging screening for 4.5–24 h. Nevertheless, certain research (such as the CHABLIS-T II study) demonstrated that the application of ultra-time window intravenous thrombolysis improves reperfusion but doesn't improve the prognosis. Therefore, multicenter trials, coupled with neuroprotective medications or anti-inflammatory therapy, and dynamic imaging stratification are required to optimize intravenous thrombolysis strategies. This article serves as a reference for clinical practice and research direction by conducting a systematic review of the recent findings on ultra-time window thrombolysis in TNK.