Effect of Admission Hyperglycemia on Safety and Efficacy of Intravenous Alteplase Before Thrombectomy in Ischemic Stroke: Post-hoc Analysis of the DIRECT-MT trial

Hyperglycemia is associated with decreased recanalization probability and increased risk of hemorrhagic complications for stroke patients treated with intravenous alteplase. However, whether hyperglycemia modifies alteplase treatment effect on clinical outcome in patients with large vessel occlusion stroke undergoing endovascular thrombectomy is uncertain. We conducted this study to determine a possible interaction effect between admission hyperglycemia and intravenous alteplase prior to thrombectomy in patients with large vessel occlusion stroke. In this post-hoc analysis of a randomized trial (DIRECT-MT) comparing intravenous alteplase before endovascular treatment vs. endovascular treatment only, 649 with available baseline glucose measurements were included. The treatment-by-admission hyperglycemia (defined as plasma glucose levels ≥ 7.8 mmol/L [140 mg/dL]) interaction was assessed using logistic regression models. As a result, among 649 patients included, 224 (34.5%) were hyperglycemic at admission. There was evidence of alteplase treatment effect modification by hyperglycemia ( P interaction = 0.025). In patients without hyperglycemia, combination therapy was associated with better outcomes compared to mechanical thrombectomy alone (adjusted common odd ratio [acOR] 1.46, 95% CI [1.04–2.07]), but not in hyperglycemic patients (acOR 0.74, 95% CI [0.46–1.20]). Combination therapy led to an absolute increase of 6% excellent outcome (mRS 0–1) in non-hyperglycemic patients (aOR 1.71, 95% CI [1.05–2.79]), but resulted in a 12.3% absolute decrease (aOR 0.42 [95% CI, 0.19–0.95] in hyperglycemic patients ( P interaction = 0.003). In conclusion, for large vessel occlusion patients directly presenting to a thrombectomy-capable hospital, hyperglycemia modified combination treatment effect on clinical outcome. Combination therapy was beneficial in patients without hyperglycemia, while thrombectomy alone may be preferred in hyperglycemic patients. Further studies are needed to confirm this result. Trial Registration Information: clinicaltrials.gov Identifier: NCT03469206.