Abstract Body: Introduction: Tenecteplase (TNK) has 14-times greater specificity for fibrin and a longer half-life compared to alteplase (ALT), offering practical advantages for ease of administration and cost effectiveness in managing acute ischemic stroke (AIS). Studies regarding safety and efficacy have shown TNK to be non-inferior to ALT, with some analyses showing greater improvements in AIS recovery with TNK compared to ALT. Our study investigated outcomes following TNK or ALT for AIS by stroke severity.

Methods: Data was collected from the TriNetX US Collaborative Network, which allowed access to de-identified retrospective electronic medical records. Patients treated with TNK or ALT for AIS after January 1, 2019 were divided into subgroups by stroke severity using the National Institutes of Health Stroke Scale (NIHSS). Patients who underwent acute mechanical thrombectomy were excluded. Propensity score matching for baseline characteristics was performed (Figure 1). Outcomes including any (asymptomatic or symptomatic) nontraumatic intracerebral hemorrhage (ICH), mortality, non-intracerebral hemorrhage, and changes in NIHSS score were assessed over 7 days from the index event. Statistical analysis was completed on the TriNetX platform.

Results: Patients with mild AIS (NIHSS 1-4) who received TNK (n=1,639) versus ALT (n=1,639) had greater risk for developing ICH (10.3% vs 7.4%, p=0.004) and worsened NIHSS score (15.8% vs 9%, p<0.0001). For moderate (NIHSS 5-15, n=1,908), moderate severe (NIHSS 16-20, n=329), or severe (NIHSS 21-42, n=372) AIS, TNK had greater likelihood for improved NIHSS score compared to ALT (moderate 14.3% vs 8.3%, p<0.0001; moderate severe 21.9% vs 14.3%, p=0.011; severe 20.2% vs 13.4%, p=0.014). For moderate to severe AIS, there was similar risk for ICH with TNK versus ALT (moderate 12.5% vs 11.2%, p=0.21; moderate severe 23.4% vs 21.6%, p=0.575; severe 26.9% vs 22.8%, p=0.203). There were no statistically significant differences in risk for mortality and non-intracerebral hemorrhage for TNK versus ALT across all NIHSS categories (Figure 2, Table 1).

Conclusion: For NIHSS ≤4, TNK was associated with higher risk of ICH and worsened stroke severity compared to ALT, suggesting ALT may be safer for mild AIS. However, TNK may be preferrable for moderate to severe AIS with NIHSS ≥5 as TNK was associated with greater likelihood for improved stroke severity with similar risks for ICH, mortality, and other non-intracerebral hemorrhages compared to ALT.