Bridging therapy increases parenchymal hemorrhage risk by 2.36 OR in patients with BGIBridging therapy may increase bleeding risk for some stroke patients

UNLABELLED: Importance Hemorrhagic transformation (HT), particularly parenchymal hematoma (PH), is a critical complication of reperfusion therapy for acute ischemic stroke, potentially offsetting the benefits of mechanical thrombectomy (MT). Whether adding intravenous thrombolysis (bridging therapy) exacerbates this risk in patients with basal ganglia infarction (BGI) remains unclear. OBJECTIVE: To assess whether bridging therapy is associated with increased PH risk in patients with acute ischemic stroke who have BGI, compared with those without. We hypothesized that bridging therapy would be associated with a higher risk of pH in patients with BGI but not in those without BGI. Design, setting, and participants This post hoc secondary analysis of the DIRECT-MT trial, a multicenter open-label randomized clinical trial, was conducted at hospitals across China from May 2018 to July 2019. Eligible patients had large-vessel occlusion acute ischemic stroke in the anterior circulation and received bridging therapy or direct MT. Of 657 patients randomized in the original trial, 607 were included after excluding those with missing imaging or incomplete follow-up. Exposures Bridging therapy (intravenous alteplase followed by MT) vs direct MT. Main outcomes and measures The primary outcome was the incidence of PH, classified per the Heidelberg Bleeding Classification. BGI was defined using a subcortical Alberta Stroke Program Early CT Score (ASPECTS) < 3 on baseline noncontrast CT. We used multivariable logistic regression including a BGI-by-treatment interaction term, adjusting for age, baseline NIHSS score, prestroke modified Rankin Scale score, onset-to-randomization time, collateral status, and cortical ASPECTS; subgroup associations were further assessed using propensity score-based weighting and doubly robust models. RESULTS: Among 607 patients (median age, 70.00 [IQR]; 43.14% female), 273 (44.98%) had BGI and 334 (55.02%) did not. The interaction between BGI status and treatment strategy was statistically significant (P for interaction = 0.04; OR, 2.80 [95% CI, 1.05-7.49]; RERI = 1.95 [95% CI, 0.40-4.42]; AP = 0.63 [95% CI, 0.15-0.94]). In the BGI subgroup, bridging therapy was associated with significantly higher PH risk vs direct MT (OR, 2.36 [95% CI, 1.24-4.51]; P = 0.009). In patients without BGI, there was no significant difference in PH risk between treatment groups (OR, 0.81 [95% CI, 0.36-1.80]; P = 0.60). Conclusions and relevance In this post hoc secondary analysis of DIRECT-MT data, bridging therapy was associated with significantly higher PH risk in patients with BGI, but not in those without. These observations suggest potential effect modification by deep infarct involvement and warrant confirmation in independent datasets and prospective studies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03469206.