The efficacy and safety of rt-PA administered as an accelerated regimen or a true bolus infusion have been evaluated both in patients with acute myocardial infarction and in patients with pulmonary embolism. Levine and coworkers carried out a double-blind randomized study in which patients with acute symptomatic pulmonary embolism who were receiving heparin were allocated to either a 2-min infusion of rt-PA at a dose of 0.6 mg/kg (33 patients) or placebo (25 patients). Perfusion lung scanning performed at 24 h showed a mean relative improvement in the perfusion defect of 37% in rt-PA-treated patients, compared with 18.8% in the placebo group (p = 0.017). By day 7, no difference in lung scan resolution was detected between the groups. The relative improvement in lung scan findings in this study appears to be of the same order of magnitude as reported in previous studies using urokinase or rt-PA infused over a long period. There were no major bleeds in either group, nor were there any differences in transfusion requirements between groups. The rt-PA-treated patients had minor bleeding, which was confined to the site of the angiography catheter or to the venipuncture sites and which was easily controlled by gentle pressure. Thus, the rt-PA bolus infusion regimen used by Levine and coworkers can provide an alternative and safe approach to thrombolytic therapy in patients with pulmonary embolism.
The therapeutic value of rt-PA bolus administration in pulmonary embolism will be compared with that of 2-h administration in a prospective, double-blind, randomized study. This study will involve more than 20 centers in the United States, Canada, and Italy. The results of this multicenter study will be crucial in assessing the potential clinical application of bolus rt-PA in venous thromboembolism.