title: Lower dosage of recombinant tissue-type plasminogen activator (rt-PA) in the treatment of acute pulmonary embolism: a systematic review and meta-analysis.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China. Electronic address: zhaizhenguo2011@126.com.
authors.forename: Zhen-guo
authors.initials: ZG
authors.lastname: Zhai
authors.affiliation: Department of Respiratory and Critical Care Medicine, Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Li-rong
authors.initials: LR
authors.lastname: Liang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Fang-fang
authors.initials: FF
authors.lastname: Liu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Yuan-hua
authors.initials: YH
authors.lastname: Yang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China; Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
mesh_terms: D004305:Dose-Response Relationship, Drug; D006801:Humans; D011655:Pulmonary Embolism / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*
chemical_list: D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator
keywords: Low dose; Pulmonary embolism; Thrombolytic therapy; rt-PA