Elevated baseline glucose and hemorrhagic complications in bridging vs direct EVT

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.

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.

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.

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.