Reduced-Dose Systemic Fibrinolysis in Massive Pulmonary Embolism: A Pilot Study

OBJECTIVE: Severe pulmonary embolism (PE) has a high mortality rate, which can be lowered by thrombolytic therapy (TT). However, full-dose TT is associated with major complications, including life-threatening bleeding. The aim of this study was to explore the efficacy and safety of extended, low-dose administration of tissue plasminogen activator (tPA) on in-hospital mortality and outcomes in massive PE. METHODS: This was a single-center, prospective cohort trial at a tertiary university hospital. A total of 37 consecutive patients with massive PE were included. A peripheral intravenous infusion was used to administer 25 mg of tPA over 6 hours. The primary endpoints were in-hospital mortality, major complications, pulmonary hypertension, and right ventricular dysfunction. The secondary endpoints were 6-month mortality and pulmonary hypertension and right ventricular dysfunction 6 months after the PE. RESULTS: The mean age of the patients was 68.76±14.54 years. The mean pulmonary artery systolic pressure (PASP; 56.51±7.34 mmHg vs. 34.16±2.81 mmHg, P<0.001) and right/left ventricle diameter (1.37±0.12 vs. 0.99±0.12, P<0.001) decreased significantly after TT. Tricuspid annular plane systolic excursion (1.43±0.33 cm vs. 2.07±0.27 cm, P<0.001), myocardial performance index (0.47±0.08 vs. 0.55±0.07, P<0.001), and systolic wave prime (9.6±2.8 vs. 15.3±2.6) increased significantly after TT. No major bleeding or stroke was observed. There was one in-hospital death and two additional deaths within 6 months. No cases of pulmonary hypertension were identified during follow-up. CONCLUSION: The results of this pilot study suggest that an extended infusion of low-dose tPA is a safe and effective therapy in patients with massive PE. This protocol was also effective in decreasing PASP and restoring right ventricular function. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02029456