Safety and efficacy of low-dose versus high-dose alteplase for pulmonary embolism: a retrospective study from MIMIC-IV

Background: Optimal dosing of alteplase for systemic thrombolysis in intermediate-risk pulmonary embolism (PE) remains controversial due to hemorrhagic risk. This retrospective cohort study analyzed data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database to evaluate dose-dependent efficacy and safety of alteplase in PE patients. Methods: Patients with PE treated with systemic alteplase thrombolysis were stratified into two groups based on a clinically established dose threshold of 50 mg. The primary outcomes included 7-day mortality and changes in hemodynamic and respiratory parameters before and after alteplase administration. Secondary outcomes included the relationship between dose stratification and mortality at the intensive care unit (ICU), hospital, 28-, 60-, and 365-day, using Kaplan-Meier survival curves and Cox proportional hazards regression. Propensity score matching (PSM) was employed to minimize bias. Results: After PSM, 122 patients were included, with 76 in the low-dose group and 46 in the high-dose group. Both groups showed improvements in heart rate (HR). In the high-dose group, partial thromboplastin time (PTT) and blood urea nitrogen (BUN) were significantly higher than in the low-dose group. The low-dose group had lower 7-day and ICU mortality rates than the high-dose group. Cox regression analysis showed that dose stratification was an independent risk factor for 7-day mortality [hazard ratio (HR): 0.289, 95% confidence interval (CI): 0.072-1.023, P=0.045]. Conclusions: This study suggests that low-dose alteplase (≤50 mg) is associated with a better balance between thrombolytic efficacy and safety.