Mild corticospinal tract injury as the optimal treatment window: argatroban efficacy stratified by corticospinal tract lesion load in branch atheromatous disease

Branch atheromatous disease (BAD) is characterized by single subcortical infarction caused by microatheroma at the orifice of a deep perforating artery, and early neurological deterioration (END) is one of its most prominent clinical features. The clinical value of the direct thrombin inhibitor argatroban in acute ischemic stroke (AIS) remains controversial, and whether the corticospinal tract (CST) modifies its treatment effect is unknown. This study aimed to evaluate the association between argatroban use and the risk of END in patients with BAD and to explore whether the treatment effect varies by the degree of CST injury. A total of 401 patients with magnetic resonance imaging (MRI)-confirmed BAD were retrospectively enrolled from the Second People’s Hospital of Chengdu (September 2020 to March 2025) and the Second Affiliated Hospital of Chongqing Medical University (January 2024 to January 2025), comprising 51 argatroban users and 350 non-users. A directed acyclic graph (DAG) was used to identify the minimal sufficient adjustment set. Inverse probability of treatment weighting (IPTW) targeting the average treatment effect on the treated (ATT) was applied, followed by three stepwise-adjusted weighted logistic regression models. Subgroup analyses were performed according to quartiles of CST lesion load (CST-LL). After weighting, standardized mean differences of all covariates were < 0.1. All three models consistently showed that argatroban use was associated with a reduced risk of END (model 3: OR = 0.43, 95% CI 0.19–0.97, P = 0.043), corresponding to an approximately 57% reduction in the odds of END. Subgroup analyses revealed a gradient attenuation of the effect with increasing CST-LL, with the most pronounced effect in the lowest CST-LL quartile (Q1: OR = 0.21, 95% CI 0.05–0.96, P = 0.044); the interaction test was not statistically significant ( P = 0.958). No symptomatic or asymptomatic intracranial hemorrhage occurred in either group during hospitalization. Argatroban use is associated with a reduced risk of END in patients with BAD, and those with mild CST injury may benefit most. This subgroup finding is hypothesis-generating and warrants confirmation in prospective randomized controlled trials.