Abstract
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.