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Marked hyperglycemia linked to higher parenchymal hematoma risk with bridging therapy versus direct EVT in strokeHigh blood sugar linked to bleeding risk after stroke clot removal procedure

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Key Takeaway
Consider direct EVT over bridging therapy in stroke patients with marked admission hyperglycemia (>11.1 mmol/L) given exploratory hematoma risk association.

This post hoc analysis of the DIRECT-MT trial (2016-2019) examined 627 patients with anterior circulation large-vessel occlusion acute ischemic stroke eligible for alteplase. It compared bridging therapy (intravenous alteplase followed by endovascular thrombectomy) with direct EVT, specifically evaluating whether admission hyperglycemia modified the risk of hemorrhagic complications.

Elevated baseline glucose was associated with greater odds of hemorrhagic transformation overall (adjusted OR 1.168 per 1 mmol/L increase, 95% CI 1.100-1.243). In the subgroup with marked hyperglycemia (glucose >11.1 mmol/L, n=71), bridging therapy was associated with significantly higher odds of parenchymal hematoma compared to direct EVT (OR 4.84, 95% CI 1.34-21.95, p=0.024). No significant differences between strategies were observed for hemorrhagic infarction or symptomatic intracranial hemorrhage.

Safety and tolerability data were not reported. Key limitations include the exploratory nature of the findings and that they apply only to EVT-eligible patients. In practice, these associations suggest that when admission glucose is markedly elevated (>11.1 mmol/L), a direct EVT strategy may warrant consideration alongside early glucose assessment and careful glycemic management, though causality cannot be inferred from this analysis.

Researchers analyzed data from 627 stroke patients who had a large blood clot blocking a major brain artery. All patients were eligible for a clot-busting drug called alteplase and underwent a mechanical clot removal procedure called endovascular thrombectomy (EVT). The study compared two treatment strategies: 'bridging therapy' (receiving the drug alteplase before the procedure) and 'direct EVT' (going straight to the procedure without the drug).

The main goal was to see if high blood sugar levels at the hospital were linked to different bleeding risks between these two treatment approaches. The analysis found that for most patients, the bleeding risks were similar. However, in a smaller group of 71 patients with very high blood sugar (over 11.1 mmol/L), those who received bridging therapy had a higher chance of developing a serious type of brain bleed called a parenchymal hematoma, compared to those who had direct EVT.

No specific safety concerns beyond this bleeding risk were reported in this analysis. It is important to be careful because this was a 'post hoc' or exploratory look at existing data, not a study designed from the start to answer this specific question. The findings only apply to stroke patients who are candidates for the clot removal procedure. Readers should understand that this research suggests doctors might need to consider a patient's blood sugar level when choosing a treatment plan, but more studies are needed to confirm this link.

What this means for you:
For stroke patients with very high blood sugar, one treatment approach may carry a higher bleeding risk than another, but more research is needed.

Study Details

Study typeRct
Sample sizen = 627
EvidenceLevel 2
PublishedApr 2026
View Original Abstract ↓
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.
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