Low-Dose vs. Standard-Dose Alteplase for Acute Ischemic Stroke: A Retrospective Cohort Study of Safety and Efficacy in an Iranian Population

Background The optimal dosing of alteplase for acute ischemic stroke remains debated, particularly regarding the balance between efficacy and bleeding risks. This study compared outcomes between standard-dose (0.9 mg/kg) and low-dose (< 0.85 mg/kg) alteplase in an Iranian cohort. Methods In this retrospective cohort study, 328 patients with acute ischemic stroke treated at Boo-Ali Sina Hospital (2016–2023) were analyzed. Participants were divided into standard-dose (n = 177) and low-dose (n = 151) groups. Primary outcomes included functional independence (modified Rankin Scale [mRS] 0–2 at 3 months) and symptomatic intracranial hemorrhage (sICH). Secondary outcomes comprised mortality and hemorrhagic complications. Multivariable logistic regression adjusted for age, NIHSS score, and comorbidities. Results The low-dose group had significantly lower rates of sICH (5.29% vs. 13.55%, p = 0.01), fatal bleeding (1.98% vs. 7.90%, p = 0.03), and in-hospital mortality (8.6% vs. 15.81%, p = 0.01). Parenchymal hemorrhage-1 occurred exclusively with standard dosing (15.9% vs. 0%). Three-month functional outcomes were comparable (mRS 0–2: 53.6% vs. 46.9%, p = 0.22). Adjusted analyses confirmed reduced odds of any ICH (OR 0.34, 95% CI 0.18–0.64) and fatal ICH (OR 0.23, 95% CI 0.06–0.83) with low-dose therapy. Conclusion Low-dose alteplase was associated with fewer hemorrhagic complications and lower mortality while maintaining comparable functional outcomes to standard dosing. These findings support its potential as a safer alternative, particularly in resource-limited settings where cost and drug availability pose challenges. Randomized trials are needed to validate these results.