(1189) Low-Dose Versus Standard-Dose Alteplase for the Treatment of High-Risk Pulmonary Embolism

Introduction: Pulmonary embolism (PE) is a common condition diagnosed in nearly 300,000 hospitalized patients in the United States per year. Alteplase is a thrombolytic indicated for treatment of high-risk PE. The optimal dosing strategy of alteplase for high-risk PE is unclear. Low-dose alteplase may be as effective and may reduce the risk of bleeding compared to standard-dose alteplase.

Methods: Retrospective cohort analysis of patients who received alteplase between June 1, 2011 and August 31, 2022 for high-risk PE. Patients were categorized based on initial dose to low-dose alteplase (50 mg) and standard-dose alteplase (100 mg). The primary outcome was hemodynamic stability within 24 hours from start of alteplase infusion, defined as discontinuation of vasoactive agents, if initiated, and systolic blood pressure greater than 90 mmHg and/or mean arterial pressure greater than or equal to 65 mmHg for at least eight consecutive hours. Secondary outcomes included in-hospital mortality, duration of mechanical ventilation, and major bleeding.

Results: One hundred twenty-four patients were screened and 65 met the inclusion criteria. Of those patients, 25 were included in the low-dose group and 40 were included in the standard-dose group. There was no difference in the primary outcome of sustained hemodynamic stability at 24 hours (32% in the low-dose group vs 37.5% in the standard-dose group P = 0.65). In-hospital mortality did not differ between groups (48% vs 45%; P = 0.81). Patients in the low-dose group experienced a shorter duration of mechanical ventilation (1.5 days vs 6 days; P = 0.03) with numerically less major bleeding (12% vs 25%; P = 0.34). No difference in other secondary outcomes were demonstrated.

Conclusions: In patients with high-risk PE a low-dose alteplase treatment strategy led to no difference in hemodynamic stability at 24 hours compared to a standard-dose alteplase treatment strategy with a trend towards reduced major bleeding. Patients in the low-dose group required significantly less days of mechanical ventilation but the clinical significance of this finding remains unclear. Future studies, ideally a large randomized controlled trial should be performed to elucidate the optimal alteplase dosing in high-risk PE.