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

Thromb Res. 2014 Mar;133(3):357-63. doi: 10.1016/j.thromres.2013.12.026. Epub 2013 Dec 23.


Background and objective: According to US Food and Drugs Administration (FDA), 2 hour recombinant tissue plasminogen activator (rt-PA) 100mg 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 100mg 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, maximum 50mg or 50mg infusion 2h) with standard dose (100mg infusion 2h). 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, maximum 50mg/2 min bolus or 10mg 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.

Keywords: Low dose; Pulmonary embolism; Thrombolytic therapy; rt-PA.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Dose-Response Relationship, Drug
  • Humans
  • Pulmonary Embolism / drug therapy*
  • Recombinant Proteins / administration & dosage
  • Thrombolytic Therapy / methods*
  • Tissue Plasminogen Activator / administration & dosage*


  • Recombinant Proteins
  • Tissue Plasminogen Activator