Abstract A005: Is Tenecteplase More Efficacious than Alteplase for Distal Occlusions? - A Secondary Analysis of the TASTE Trial

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Introduction: Landmark clinical trials have examined the safety and efficacy of tenecteplase, demonstrating non-inferiority when compared to intravenous alteplase in the < 4.5hr time window. Sub-analysis of tenecteplase performance in large and medium sized occlusions have been performed. However, the efficacy of tenecteplase in patients with more distal occlusions, such as those in the distal branches of the middle cerebral artery (MCA), in the anterior (ACA), or posterior cerebral artery (PCA) territories, is unknown. Methods: We performed a pre-planned imaging analysis of TASTE, a multicenter randomized trial of tenecteplase and alteplase in patients presenting within 4.5hrs of symptom onset with perfusion imaging-confirmed stroke and evidence of target mismatch (penumbra/core ratio >1.8 and an absolute difference >15 mL) on CT perfusion. Occlusion site was categorized into: ICA + proximal M1, distal M1, proximal M2, distal M2, M3 and beyond, ACA, and PCA. Patients enrolled into TASTE did not receive endovascular therapy. Primary outcome was mRS 0-1 at 90 days. The treatment effect of tenecteplase and alteplase was compared, stratifying by occlusion site, and adjusting for age, baseline NIHSS and pre-morbid mRS in modified Poisson regression models. Results: Of the 601 patients included in the primary analysis, 295 (49%) received tenecteplase and 306 (51%) received alteplase. Tenecteplase was associated with a higher odds of mRS 0-1 with distal (M3 and beyond) occlusions (tenecteplase: 62/81 [76%] vs. alteplase: 59/93 [63%], aRR: 1.23 [95% CI: 1.04-1.46]). Rates of 90-day mRS 0-1 were comparable for proximal M2 (tenecteplase: 27/48 [56%] vs. alteplase: 29/50 [58%], aRR: 1.02 [95% CI: 0.74-1.41]) and distal M2 occlusions (tenecteplase: 30/46 [65%] vs. alteplase: 28/48 [58%], aRR: 1.14 [95% CI: 0.84-1.54]). No difference in tenecteplase treatment effect was observed for anterior (tenecteplase: 12//21 [57%] vs. alteplase: 5/13 [38%], aRR: 1.45 [95% CI: 0.70-2.99]) or posterior cerebral artery (tenecteplase: 21/46 [46%] vs. alteplase: 22/46 [47%], aRR: 0.92 [95% CI: 0.62-1.36]) occlusions. Conclusion: Patients with more distal MCA occlusions (M3 and beyond) who are treated with tenecteplase are more likely to achieve mRS 0-1 at 90 days than those treated with alteplase. Differences in treatment effect with more proximal MCA and posterior cerebral artery occlusions were not observed.

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