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A Multicenter Study of Pulmonary Embolism Patients Treated With Reduced- or Full-Dose Alteplase

Sunday, January 21, 2024
3:10 PM – 3:20 PM MT
Location: Connections Central - Star Research Theater
Introduction: Systemic thrombolysis improves outcomes in pulmonary embolism (PE) patients but is associated with the risk of hemorrhage. There is limited information on how reduced-dose alteplase compares to the full-dose regimen regarding clinical outcomes and complications. We hypothesized that a reduced-dose regimen results in similar efficacy and less hemorrhagic complications.


Methods: This was a multi-center retrospective study of patients hospitalized (January 1, 2012 - December 31, 2020) with PE and treated with systemic alteplase. Pre- and post-alteplase hemodynamic and respiratory variables, patient outcomes, and complications were compared between dose regimens using a Wilcoxon rank sum test for continuous data, and a Chi-square test for categorical variables.


Results: Ninety-eight patients were treated with full-dose (100 mg) and 186 with reduced-dose (50 mg) regimens. Following alteplase, significant improvements in mean shock index (1.37 to 1.10 and 1.07 to 0.79 for full- and reduced-dose cohorts respectively, P < 0.001 for both), blood pressure, heart rate, respiratory rate, and supplemental O2 requirement were observed in both groups. Hemorrhagic complications were lower with the reduced- compared to the full-dose regimen (13% vs. 24.5%, P=0.014), and most were minor. Major extracranial hemorrhage occurred in 1.1% vs. 6.1% respectively (P=0.022). Complications were associated with supratherapeutic levels of heparin anticoagulation in 37.5% and invasive procedures in 31.3% of cases. The differences in complications persisted after propensity score (PS) weighting (15.4% vs 24.7%, p=0.12 and 1.3% vs 7.1%, p=0.067), but didn’t reach statistical significance. There were no significant differences in mortality, discharge destination, ICU or hospital length of stay, or readmission after PS weighting.


Conclusions: Systemic thrombolysis provides an effective mode of reperfusion therapy in PE patients, resulting in improved hemodynamic and respiratory parameters. When compared to the full-dose, reduced-dose alteplase results in similar outcomes but fewer hemorrhagic complications. Heparin management strategies preventing excessive levels of anticoagulation and avoidance of invasive procedures should be considered to further reduce complications.