Abstract

Introduction Thrombolysis with recombinant tissue plasminogen activator remains vital to acute ischemic stroke (AIS) therapy. Several centers in the United States are adopting Tenecteplase (TNK) over Alteplase (ALT) due to its ease of administration, fibrin specificity, longer half‐life, and non‐inferiority of TNK compared to ALT [1‐2]. In this study, we investigated whether there is any difference in clinical outcomes among patients undergoing endovascular therapy (EVT) pretreated with ALT vs. TNK. Methods This is a single‐center retrospective study of patients presenting with AIS between January 1, 2020 and December 31, 2022, and treated with either ALT or TNK that subsequently underwent EVT. Non‐parametric tests were used to compare differences between ALT and TNK groups. A p‐value of <0.05 was considered statistically significant. Effect size is reported using Hedges’ G statistic, and the sample size is calculated to estimate the study cohort needed for a randomized controlled trial using real‐world practice data. Results During the study period, 165 patients were treated with ALT, and 64 patients were treated with TNK. There was no difference between the ALT and TNK cohorts in their baseline demographic characteristics or premorbid vascular risk factors. Of the 165 patients undergoing thrombolysis, 75 also underwent EVT, with 55 patients treated with ALT compared to 20 patients treated with TNK. The admission National Institutes of Health Stroke Scale scores (NIHSS) were similar. Although the time of symptom onset to thrombolysis was faster in the TNK group, it was not statistically different from the ALT group. Time to EVT from symptom onset was faster in the TNK group (median time 391.0 vs. 190.0 min, p=0.00021). However, discharge NIHSS was not statistically different (mild [18 (34.0%) vs. 9 (47.4%)], moderate [10 (18.0%) vs. 1 (5.3%)], moderate to severe [13 (24.5%) vs. 4 (21.1%)], severe [12 (22.6%) vs. 5 (26.3%)], p=0.472). Using NIHSS (16 and above) as the outcome of interest – it is noted that the number needed to treat (NNT) in this subgroup was ‐27. This implies that when TNK is used as a thrombolytic therapy before EVT, it will result in one additional adverse event (NIHSS of 16 and above) compared to ALT. Comparing ALT and TNK patients undergoing EVT according to their 3‐month mRS, an effect size of 0.274 is noted using Hedges’ G, indicative of a small to moderate effect size. It would require 478 patients (with 239 in each group) to detect a difference that the randomness in our current cohort may otherwise mask. Conclusion Despite several practical advantages and faster treatment with TNK, our study failed to provide evidence of its superiority compared to ALT in patients undergoing EVT. Furthermore, we noted a potential harm among TNK‐treated patients compared to ALT. This observation needs further investigation to determine if certain local and systemic factors might contribute to TNK’s adverse outcome profile in the EVT population despite its pharmacological superiority compared to ALT.

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