P5591Efficacy and safety of lower dose slow infusion of t-PA for intermediate-risk pulmonary embolism patients with risk for bleeding

Abstract

Abstract Background Current guidelines do not recommend thrombolytic therapy for the treatment of intermediate-risk pulmonary embolism (PE) because of the tight balance between the benefit and safety with classic protocols. Aim The aim of this study was to compare the new thrombolytic protocol with lower-dose slow-infusion (LDSI) of tissue plasminogen activator (tPA) to classic 2-hours tPA infusion protocol or no-reperfusion in patients with intermediate-high risk PE with higher bleeding risk regarding 30-day efficacy and safety. Methods Among 849 patients with PE from the Serbian multicenter registry, 469 patients who fulfilled criteria for intermediate-risk PE were involved in the study. After propensity score matching 425 patients [263 (61.9%), 99 (23.3%) and 63 (14.8%) were treated with no-reperfusion, classic tPA protocol (100 mg for 2 hours) and LDSI of tPA (2–5 mg/hour either vie local catheter or systemic venous infusion with dose range of 25–50 mg)]. The basic characteristics of patients were well balanced between groups except that patients treated with LDSI of tPA had significantly higher usage of drugs which can be associated to bleeding and more previous bleeding events. Thirty day all-cause and PE-caused mortality and 7-day major bleeding were the main efficacy and safety end-points, respectively. Results All-cause and PE-cause 30-day mortality were 8.7% vs 16.2% vs 1.6% (Log rank p=0.007) and 4.5% vs 11.0% vs 0.0% (Log rank p=0.008) in patients with no-reperfusion, classic tPA protocol and LDSI of tPA protocol, respectively. Major bleeding at 7 days were 2.7% vs 8.1% vs 14.3% (Log rank p=0.001) in patients with no-reperfusion, classic tPA protocol and LDSI of tPA protocol, respectively. There was one fatal intracranial bleeding during catheter infusion of tPA. Conclusion Lower-dose slow-infusion of tPA protocol decreased significantly all-cause and PE-cause mortality at 30-day at the cost of excess of non-fatal major bleeding at 7-day in patients with intermediate-risk PE and higher risk for bleeding. Acknowledgement/Funding None