Tirofiban-Nimodipine Combination Therapy for Early NeurologicalDeterioration in Small Artery Occlusion Stroke: A Retrospective CohortStudy

INTRODUCTION: Early neurological deterioration (END) affects approximately 30% of patients with small artery occlusion (SAO) stroke. The combination of tirofiban and nimodipine may simultaneously address microthrombosis and vasospasm, two key mechanisms underlying SAOrelated END. METHODS: In this retrospective cohort study, we analyzed data from consecutive SAO-END patients treated within two hours of END onset between January 2023 and December 2024. The combination group (n=50) received tirofiban plus nimodipine, while the control group (n=53) received tirofiban alone. The primary outcome was early neurological improvement (ENI), defined as a ≥ 2-point reduction in NIHSS score or ≥ 1-point improvement in motor function at 7 days or discharge. Secondary outcomes included a favorable functional outcome (mRS ≤2) at 90 days and safety events. RESULTS: The combination group demonstrated significantly higher rates of ENI (76% vs. 47.2%; adjusted odds ratio [aOR] 3.96, 95% CI 1.32-11.90; p=0.014) and improved 90-day functional outcomes (84% vs. 58.5%; aOR 4.744, 95% CI 1.212-18.567; p=0.025). Higher admission NIHSS scores (aOR 0.759, 95% CI 0.612-0.941; p=0.012) and diabetes (aOR 0.201, 95% CI 0.048-0.840; p=0.028) were inversely associated with ENI. Older age (aOR 0.933, 95% CI 0.876-0.994; p=0.032) and higher admission NIHSS score (aOR 0.592, 95% CI 0.447-0.784; p=0.000) were negatively correlated with 90-day outcomes. Safety profiles were comparable between groups, with no instances of intracranial hemorrhage or hypotension. The addition of nimodipine did not significantly affect blood pressure. DISCUSSION: Combining tirofiban and nimodipine may improve outcomes in SAO-related early neurological deterioration. If validated in future randomized trials, this combination could address a significant unmet need in a common stroke subtype with high risk of deterioration, potentially influencing clinical practice and guiding further research into multimodal neuroprotection strategies for cerebral small vessel disease. CONCLUSION: Tirofiban-nimodipine combination therapy was found to be associated with enhanced early neurological recovery in SAO-END patients, warranting further investigation through larger multicenter randomized controlled trials.