The Evaluation of Tenecteplase for the Treatment of an Ischemic Stroke

IntroductionFor more than two decades, the standard for thrombolysis for Acute Ischemic Stroke (AIS) has been alteplase 0.9 mg/kg (maximum 90 mg) with 10 % given as a bolus. More recent studies such as the EXTEND-IA, and AcT study have shown tenecteplase (TNK) may have potential advantages over alteplase for AIS. In November 2024 the ATTEST-2 study was published with the largest comparative prospective study to date. This study included 1858 patients from 39 stroke centers in the UK which were randomized to receive TNK 0.25 mg/kg IV or alteplase standard of care dose. The study showed TNK was non-inferior to alteplase for 90-day mRS (p<0.001). On March 3rd, 2025, the FDA approved TNK for AIS based off the AcT trial. This study further evaluates the effectiveness and safety of TNK at 0.25 mg/kg IV for AIS and represents real world community hospital utilization covering a diverse population reinforcing the safety and efficacy of TNK compared with alteplase. MethodsThe analysis used a multicenter, retrospective cohort study across 11 primary and comprehensive hospitals within the BayCare Health System in West Central Florida (December 2019-April 2024), comparing TNK 0.25 mg/kg (max 25 mg) with standard-dose alteplase among adults with AIS presenting within 4.5 hours of last-known-well. The primary outcome (LVO subgroup) was substantial early reperfusion prior to thrombectomy (mTICI 2b/2c/3 or absence of retrievable thrombus). Key secondary outcomes included door-to-needle time, admission, and discharge NIHSS and 90-day mRS, and safety (ICH, angioedema). Adjusted analyses used logistic and ordinal logistic regression. ResultsAmong 476 AIS patients (TNK n=270; alteplase n=206), 226 had LVO (TNK n=115; alteplase n=111). Early reperfusion occurred in 14.8% with TNK vs 4.5% with alteplase (risk difference 10.3% [95% CI, 2.7-17.8], p=0.008). Adjusted odds of early reperfusion were higher with TNK (OR 3.53 [95% CI, 1.20-10.40], p=0.022). In all AIS patients, median door-to-needle time was shorter with TNK (34 vs 45 minutes; difference -11 [95% CI, -14.4 to -7.6], p<0.001). Good 90-day functional outcome (mRS 0-2) was more common with TNK among LVO patients (47.3% vs 29.3%, p=0.031) and among all AIS patients (61.8% vs 50.0%, difference 11.8% [95% CI, -0.3 to 23.4], p=0.044). Symptomatic ICH and angioedema were similar; across all patients combined, ICH (symptomatic and asymptomatic) was less frequent with TNK (8.5% vs 15.0%, p=0.030). ConclusionIn routine practice, TNK 0.25 mg/kg was associated with higher pre-thrombectomy reperfusion in LVO, shorter door-to-needle times, comparable safety, and improved functional outcomes versus alteplase in key analyses. These findings align with recent randomized evidence and support TNK as an effective alternative to alteplase for AIS.