Lower dosage of recombinant tissue-type plasminogen activator (rt-PA) in the treatment of acute pulmonary embolism: A systematic review and meta-analysis

Background and Objective: According to US Food and Drugs Administration (FDA), 2 hour recombinant tissue plasminogen activator (rt-PA) 100 mg infusion is recommended for eligible patients with acute pulmonary embolism (PE). However, there exists evidence implying that a lower dosage of rt-PA can be equally effective but potentially safer compared with rt-PA 100 mg regimen. The aim of this systematic review and meta-analysis is to assess the efficacy and safety of low dose rt-PA in the treatment of acute PE. Material and Method: We searched Pubmed, EMBASE, the Cochrane library and CBM Literature Database for randomized controlled trials (RCT) focusing on low dose rt-PA for acute PE. Outcomes were described in terms of changes of image tests and echocardiography, major bleeding events, all-cause death, and recurrence of PE. Results: Five studies (440 patients) were included, three of which compared low dose rt-PA (0.6 mg/kg, maximum50 mg or 50 mg infusion 2 h) with standard dose (100 mg infusion 2 h). There were more major bleeding events in standard dose rt-PA group than in low dose group (OR 0.33, 95% CI 0.12-0.91; P = 0.94, I-2 = 0%), while there were no statistical differences in recurrent PE or all cause mortality between these two groups. Two studies compared low dose (0.6 mg/kg, maximum50 mg/2 min bolus or 10 mg bolus,= 40 mg/2 h) with heparin. There was no significant difference in major bleeding events (OR 0.73, 95% CI 0.14-3.98; P = 0.72), recurrent PE or all cause mortality. No dose-related heterogeneity was found for all the included studies. Conclusions: The results of this meta-analysis were hypothesis-generating. Based on the limited data, our systematic review suggested that low dose rt-PA had similar efficacy but was safer than standard dose of rt-PA. In addition, compared with heparin, low dose rt-PA didn't increase the risk of major bleeding for eligible PE patients. (C) 2013 Elsevier Ltd. All rights reserved.