Efficacy and safety of treatment strategies for early neurological deterioration after acute ischemic stroke: a network meta-analysis of randomized controlled trials

BACKGROUND: Early neurological deterioration (END) is a serious complication of acute ischemic stroke and may occur spontaneously or after reperfusion therapy. OBJECTIVE: To compare the efficacy and safety of different interventions for acute ischemic stroke patients with END using network meta-analysis. METHODS: Randomized controlled trials were identified through systematic searches of major databases up to February 2026. The primary outcome was the 90-day modified Rankin Scale score. Secondary outcomes included neurological improvement (assessed by NIHSS), intracranial hemorrhage, and mortality. RESULTS: Five randomized controlled trials including 1,164 patients were analyzed. Compared with standard antiplatelet therapy (ST; which included aspirin monotherapy, placebo plus aspirin, or dual antiplatelet therapy depending on the study protocol), indobufen combined with ST, and tirofiban combined with ST, significantly improved 90-day functional outcome, whereas argatroban combined with standard treatment reduced mean mRS scores but did not significantly increase the proportion of patients achieving favorable functional outcomes (mRS 0-2) or excellent functional outcomes (mRS 0-1). Indobufen demonstrated the highest probability of being the optimal treatment for reducing the mean 90-day mRS score and improving 90-day NIHSS scores based on SUCRA rankings. Indobufen and tirofiban (each added to ST) also significantly improved neurological recovery at short- and long-term follow-up. However, argatroban and tirofiban did not significantly increase the proportion of patients achieving favorable functional outcomes. None of the interventions increased the risk of intracranial or symptomatic hemorrhage. CONCLUSIONS: Indobufen was associated with lower mean 90-day mRS and NIHSS scores, whereas tirofiban added to standard antiplatelet therapy increased the proportion of patients achieving a favorable functional outcome defined as mRS 0-2. Neither tirofiban nor argatroban significantly increased the proportion achieving an excellent functional outcome defined as mRS 0-1. These findings should be interpreted cautiously because of the limited number and size of the included trials.