ABSTRACT Background Acute ischemic stroke (AIS) accounts for 87% of all strokes and is associated with high morbidity and mortality. Stroke mimics, conditions that present with stroke‐like symptoms but are not AIS, represent an important proportion of stroke cases. Tenecteplase, an alteplase variant with higher fibrin affinity and a longer half‐life, has recently gained approval for the treatment of AIS. Limited evidence exists on the safety of tenecteplase in stroke mimics. Objective The objective of this study was to determine the incidence of intracranial hemorrhage in patients with stroke‐like signs and symptoms who received tenecteplase with and without a confirmed diagnosis of AIS. Methods This was a single‐center, retrospective cohort study conducted at a comprehensive stroke center. Patients who received tenecteplase for stroke‐like symptoms from June 2020 to December 2021 were included. Patients were grouped based on AIS diagnosis confirmed by neuroimaging or discharge diagnosis. The primary outcome was the incidence of intracranial hemorrhage, and secondary outcomes included incidence of symptomatic and asymptomatic intracranial hemorrhage, extracranial hemorrhage, hospital length of stay, angioedema development, and discharge disposition. Results Of 250 patients, 174 were diagnosed with AIS and 76 with stroke mimics. Patients with AIS were older (69 years SD: 13.8 years vs. 62.3 years SD: 16.1 years; p = 0.0008), had higher hypertension prevalence (132 75.9% vs. 44 57.9%; p = 0.0042), and lower previous stroke prevalence (9 5.2% vs. 11 14.5%; p = 0.0126) compared with stroke‐mimic patients, respectively. Patients with AIS had shorter median tenecteplase door‐to‐needle times (38.5 min IQR: 30 min, 53 min vs. 46.5 min IQR: 34.5 min, 64.5 min; p = 0.0154) compared with stroke mimics. Intracranial hemorrhage occurred in 11.5% of patients with AIS and none in stroke mimics ( p = 0.0021). Symptomatic hemorrhage rates were similar between groups. Patients with AIS had longer median hospital stays (3 days IQR: 2 days, 6 days vs. 2 days IQR: 2 days, 4 days; p = 0.0018). Discharge dispositions and cases of angioedema were similar between groups. Conclusion Tenecteplase appears safe for stroke mimics, with no disproportionate harm compared to patients with AIS. This study further supports the safety of tenecteplase in stroke mimics, aiding rapid treatment decisions in stroke‐like presentations.
Rowe et al. (2026) studied this question.