Recombinant tissue-type plasminogen activator versus a novel dosing regimen of urokinase in acute pulmonary embolism: a randomized controlled multicenter trial

Abstract

Thrombolysis of acute pulmonary embolism can be accomplished more rapidly and safely with 100 mg of recombinant human tissue-type plasminogen activator (rt-PA) (Activase) than with a conventional dose of urokinase (Abbokinase) given as a 4,400-U/kg bolus dose, followed by 4,400 U/kg per h for 24 h. To determine the effects of a more concentrated urokinase dose administered over a shorter time course, this trial enrolled 90 patients with baseline perfusion lung scans and angiographically documented pulmonary embolism. They were randomized to receive either 100 mg/2 h of rt-PA or a novel dosing regimen of urokinase: 3 million U/2 h with the initial 1 million U given as a bolus injection over 10 min. Both drugs were delivered through a peripheral vein. To assess efficacy after initiation of therapy, repeat pulmonary angiograms at 2 h were performed in 87 patients and then graded in a blinded manner by a panel of six investigators. Of the 42 patients allocated to rt-PA therapy, 79% showed angiographic improvement at 2 h, compared with 67% of the 45 patients randomized to urokinase therapy (95% confidence interval for the difference in these proportions [rt-PA minus urokinase] is -6.6% to 30.4%; p = 0.11). The mean change in perfusion lung scans between baseline and 24 h was similar for both treatments. Three patients (two treated with rt-PA and one with urokinase) had an intracranial hemorrhage, which was fatal in one. The results indicate that a 2-h regimen of rt-PA and a new dosing regimen of urokinase exhibit similar efficacy and safety for treatment of acute pulmonary embolism.

A critical review of thromboembolic complications associated with central venous catheters

“…Evidence from RCTs, reporting on patients with massive [49][50][51][52][53][54] and submassive 52,55 PE, favour thrombolysis over heparinization. Randomized controlled trials comparing streptokinase and alteplase, in massive PE, 56,57 and urokinase and rTPA 58 failed to demonstrate superiority of one thrombolytic over another. The major risks associated with pulmonary thrombolysis include bleeding, hematoma formation at puncture sites, and intracranial hemorrhage, with intracranial hemorrhage occurring in approximately 2% of patients, ensuing up to 14 days following thrombolysis.…”

Long-term benefit of thrombolytic therapy in patients with pulmonary embolism

“…[3][4][5][6][7] All three of the above thrombolytic agents have been proven to be superior to heparin in the early resolution of a clot in the pulmonary vasculature as evaluated by pulmonary angiography and perfusion lung-scanning. The resultant improvement in right ventricular function has been confirmed by hemodynamic measurements 8 and by two-dimensional echocardiography.…”

The role of thrombolytic therapy in pulmonary embolism

“…[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] An additional 16 studies compared different types of thrombolytic agents, and included a total of 1244 patients (supplemental Appendix 5). [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] One study (Ultrasound-Accelerated Thrombolysis of Pulmonary Embolism [ULTIMA] trial) investigated catheter-directed thrombolysis (CDT), and enrolled a total of 59 patients. 42 All studies were randomized, but only 7 were clearly blinded.…”