Marked hyperglycemia linked to higher parenchymal hematoma risk with bridging therapy versus direct EVT in stroke

BACKGROUND: Hyperglycemia on admission is associated with heightened hemorrhagic risk in acute ischemic stroke (AIS), but whether this risk association differs between bridging therapy (intravenous alteplase followed by endovascular thrombectomy [EVT]) and direct EVT remains unclear. METHODS: This post hoc analysis of the DIRECT-MT trial (2016-2019) included 627 patients with anterior circulation large-vessel occlusion AIS eligible for alteplase from multiple centers. Baseline glucose levels were assessed, and hemorrhagic outcomes followed the Heidelberg scheme: hemorrhagic transformation (HT; radiologic umbrella that includes hemorrhagic infarction [HI] and parenchymatous hematoma [PH]) and symptomatic intracranial hemorrhage (sICH). Logistic regression and restricted cubic spline models evaluated glucose-hemorrhage associations and the treatment-by-glucose interactions. RESULTS: Median age was 69 years (43 % female), with median baseline glucose of 7.8 mmol/L. Elevated glucose was associated with greater odds ofhemorrhagic transformation (HT)(adjusted OR1.168per 1 mmol/L; 95 % CI,1.100-1.243). A significant interaction indicated higher hemorrhagic risk with bridging therapy versus direct EVT at glucose levels > 11.1 mmol/L. In the > 11.1 mmol/L subgroup (n = 71), bridging therapy was associated with increased PH risk (OR 4.84; 95 % CI 1.34-21.95, p = 0.024), whereas no excess risk was seen at ≤ 11.1 mmol/L. No significant differences were observed for HI or sICH. CONCLUSION: Admission hyperglycemia was associated with higher odds of hemorrhagic complications in AIS patients undergoing EVT. In patients with marked admission hyperglycemia (>11.1 mmol/L), bridging therapy was associated with higher odds of parenchymal hematoma than direct EVT, whereas no excess risk was observed at lower glucose levels. These exploratory findings apply only to EVT-eligible patients and primarily inform the choice between bridging therapy and direct EVT, suggesting that, when blood glucose is markedly elevated, a direct EVT strategy may warrant consideration alongside early glucose assessment and careful glycemic management.