Abstract Body: Introduction:
Tenecteplase (TNK) is now an accepted alternative to Alteplase (ALT) for intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). Hemorrhagic transformation (HT), a complication of IVT, is more frequent in acute hyperglycemia and diabetes (DM) and is associated with poor clinical outcomes. We previously reported better clinical outcomes in DM patients treated with TNK. In this study we explored if HT is associated with the observed less favorable outcomes in ALT-treated DM patients.

Methods:
In this 4-year retrospective cohort of AIS patients from 2 comprehensive stroke centers, DM was defined by known history, antidiabetic medication use, and admission glycated hemoglobin ≥6.5%. Time to IVT was grouped as ultra-early (0-90 min), early (91-180 min), and late (181-270 min). Peripheral blood indices, neutrophil to lymphocyte ratio (NLR), and systemic immune inflammation index (SII) were used to assess acute immune response at admission and 24 hours. Non-parametric tests compared intergroup differences with statistical significance at p-value <0.05.

Results: Three hundred and twelve patients (ALT, n=165 [DM, n=63; non-DM, n=102]; TNK, n=147 [DM, n=48; non-DM, n=99]) were included. The distribution was similar across groups of time to IVT between ALT and TNK (ultra-early [ALT, n=30%; TNK, n=36%]; early [ALT, n=51%; TNK, n=48%]; late [ALT, n=20%; TNK, n=17%], p=0.5). Baseline characteristics were similar between DM and non-DM within IVT groups. Rise in NLR at 24 hours was higher in non-DM ALT-treated patients compared to DM (109 [21, 262] vs. 45 [-14, 217], p=0.039), though other inflammatory markers were similar. HT was lower in non-DM compared to DM (17% vs. 33%, p=0.013) ALT-treated patients, though similar among TNK-treated patients. There were no differences in inflammatory markers or rates of HT in ultra-early or late periods. In the early period, non-DM TNK-treated patients experienced a higher rise in NLR (163 [60, 492] vs. 25 [-8, 168], p=0.015) and SII (134 [56, 447] vs. 28 [-8, 128], p=0.019) at 24 hours compared to DM, though HT rates were similar. In the early ALT cohort, DM experienced higher HT (33% vs. 12%, p=0.021).

Conclusions:
There was a higher rate of HT in ALT-treated DM patients compared to non-DM when administered at 91-180 min. This difference was not seen in ultra-early or late ALT administration or with TNK. Larger studies will need to validate these findings and clarify the role of early inflammation in mediating HT.