Efficacy and safety of 2-hour urokinase regime in acute pulmonary embolism: a randomized controlled trial

Chen Wang,Lirong Liang,Yadong Yuan,Xiansheng Cheng,Zhenguo Zhai,Ying H Shen,Huaping Dai,Zhonghe Zhang,Zhaozhong Cheng,Yuanhua Yang,Kewu Huang,Weixuan Lu

doi:10.1186/1465-9921-10-128

Abstract

BackgroundsUrokinase (UK) 2 200 U/kg·h for 12 hours infusion(UK-12 h)is an ACCP recommended regimen in treating acute pulmonary embolism (PE). It is unclear whether this dose and time can be reduced further. We compared the efficacy and safety of 20, 000 U/kg for 2 hours (UK-2 h) with the UK-12 h regime in selected PE patients.MethodsA randomized trial involving 129 patients was conducted. Patients with acute PE were randomly assigned to receive either UK-12 h (n = 70), or UK-2 h (n = 59). The efficacy was determined by the improvement of right heart dysfunction and perfusion defect at 24 h and 14 d post UK treatment. The bleeding incidence, death rate and PE recurrence were also evaluated.ResultsSimilarly significant improvements in right heart dysfunction and lung perfusion defects were observed in both groups. Overall bleeding incidents were low in both groups. Major bleeding directly associated with UK infusion occurred in one patient in the UK-2 h group and one in the UK-12 h group. Mortality rates were low, with one reported fatal recurrent in the UK-12 h group and none in the UK-2 h group. When the rate of bleeding, death and PE recurrence were compared separately in the hemodynamic instability and the massive anatomic obstruction subgroups, no significant difference was found.ConclusionsThe UK-2 h regimen exhibits similar efficacy and safety as the UK-12 h regimen for acute PE.Trial RegistrationClinical trial registered with http://clinicaltrials.gov/ct2/show/NCT00799968 (Identifier: NCT 00799968)

Highlights

Urokinase (UK) can produce mild and prolonged thrombolytic state with minimal disturbance of blood coagulation
Patient population and baseline characteristics 137 patients with acute pulmonary embolism (PE) were preselected in the participating centers. 125 patients were confirmed with CT pulmonary angiograms (CTPA). 98 patients were evaluated with V/Q at the same time. 8 (7%) were ineligible because of the predefined exclusion criteria
Our study showed that the U/kg for 2 hours (UK-2 h) regimen exhibited similar efficacy as the UK-12 h regimen in PE thrombolytic therapy, with similar progressive improvements in pulmonary perfusion defects and right ventricular dysfunction (RVD) during the 14 d posttreatment period

Summary

Introduction

Urokinase (UK) can produce mild and prolonged thrombolytic state with minimal disturbance of blood coagulation. A loading dose of 4400 IU/kg followed by 2200 IU/kg/hour for 12 hours (UK-12 h) is recommended for acute PE treatment by American College of Chest Physician (ACCP) guideline[3]. Earlier studies have showed that the bleeding incidence of this regimen was high [4,5]. We have observed that the UK-2 h (20 000 U/kg over 2 h) regime has superior thrombolytic effects over the UK-12 h regimen for fresh thrombi in a canine PE model [6]. Because of the potential advantages of lower bleeding risk, increased effectiveness for fresh thrombi, convenience and lower cost, UK-2 h becomes a promising regimen. There is no direct comparison between this regimen with the ACCP recommended UK12 h regimen

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Conclusion