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

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.