Standard-dose tPA vs. slow-infusion tPA vs. catheter-guided low-dose tPA in the treatment of patients with intermediate-high-risk pulmonary embolism

Abstract Background Fibrinolysis is recommended for patients with intermediate-high-risk acute pulmonary embolism (PE) when hemodynamic collapse is anticipated. The standard protocol involves systemic infusion of 100 mg of tissue plasminogen activator (tPA) over two hours. However, catheter-guided fibrinolysis with a lower tPA dose is also an available treatment option, while slow systemic infusion with a reduced tPA dose is rarely used. Purpose This study aimed to compare the 30-day mortality rate and 7-day bleeding rate among three fibrinolytic treatment protocols in consecutive patients with intermediate-high-risk PE. Methods This retrospective cross-sectional study included consecutive PE patients from a regional PE registry. Only patients with intermediate-high-risk PE—defined as systolic blood pressure above 90 mmHg with elevated troponin levels and imaging evidence of right ventricular strain—were included. In addition, only patients received one of three fibrinolytic treatment protocols using tPA, were included. The standard-dose tPA group received a 100 mg IV infusion over two hours. The catheter-guided fibrinolysis group received tPA directly into the pulmonary artery obstructed by thrombus, with a reduced dose (typically ≤30 mg, infused at 2–2.5 mg/h) via a standard pig-tail catheter, or with an ultrasound assisted device. The slow-infusion low-dose tPA group received no more than 50 mg of tPA via IV infusion at a rate of 2.5–5 mg/h. The 30-day mortality rate was assessed using Kaplan-Meier curves. The 7-day bleeding rate was compared between the groups, along with bleeding risk, which was assessed using the Pulmonary Embolism Bleeding Severity Index (PEBSI). A PEBSI score ≥2 indicated high bleeding risk. Results Of the 2,318 patients in the registry, 310 met the inclusion criteria. Standard-dose tPA was administered to 125 patients (40.3%), catheter-guided low-dose tPA to 88 patients (28.4%), and slow-infusion tPA to 97 patients (31.3%). The 30-day mortality rate was highest in the standard-dose tPA group and lowest in the slow-infusion tPA group (log-rank p=0.007). Baseline demographic, laboratory, and clinical characteristics were comparable across groups, except for right ventricular systolic pressure, which was significantly higher in the catheter-guided low-dose tPA group (60±15 mmHg) compared to the standard-dose (50±15 mmHg) and slow-infusion (55±15 mmHg) groups. Despite differences in bleeding risk (p=0.020), with the highest risk in the slow-infusion group (p=0.039 compared to the standard-dose group), the 7-day bleeding rate did not significantly differ between groups. Conclusion In patients with intermediate-high-risk PE, the standard-dose tPA group had a significantly higher early mortality rate compared to the catheter-guided low-dose tPA and slow-infusion tPA groups. Despite the significantly higher bleeding risk in the slow-infusion group, bleeding rates did not differ significantly between groups.The 30-day mortality difference The 7-day bleeding difference