Background: In patients with acute ischemic stroke (AIS), tenecteplase and alteplase help preserve brain tissue. The 2019 American Heart Association/American Stroke Association guidelines designate alteplase as the first-line therapy for AIS, listing tenecteplase as a reasonable alternative for patients eligible for mechanical thrombectomy. The 2023 European Stroke Organisation recommends tenecteplase in patients with AIS due to large vessel occlusion prior to thrombectomy. Our institution adopted tenecteplase as the formulary fibrinolytic for AIS due to emerging clinical data, reduced cost, and operational benefits. Objective: The objective was to compare outcomes associated with tenecteplase versus alteplase in AIS. Methods: This multicenter, retrospective study included adults treated with tenecteplase or alteplase for AIS between April 1, 2022 and April 1, 2023. The primary outcome was intracranial hemorrhage (ICH) within 36 hours. Secondary outcomes included hospital and intensive care unit length of stay, in-hospital all-cause mortality, door-to-needle time, time to reperfusion, and adverse events. A subgroup analysis was performed to assess ICH that required reversal therapies. Results: There was no significant difference in the incidence of ICH between the tenecteplase and alteplase groups (20.4% vs 11.7%; P = 0.09). Within the subgroup analysis, a higher proportion of patients in the tenecteplase group required reversal therapies for ICH compared with the alteplase group (35.0% vs 8.3%; P = 0.09). Secondary outcomes were similar between groups. Conclusion: There was no significant difference in the incidence of ICH after tenecteplase or alteplase administration. Further studies are warranted to clarify the comparative safety profiles of tenecteplase and alteplase.
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