title: Tissue plasminogen activator for the treatment of deep venous thrombosis of the lower extremity: a systematic review.
abstract: OBJECTIVE
  To assess, by systematic review, the efficacy and safety of recombinant tissue plasminogen activator (rt-PA) in the treatment of lower extremity deep venous thrombosis (DVT). A secondary objective is to assess the optimal dose and route of administration of rt-PA.
  
  
  METHODS
  Included studies were randomized, controlled trials comparing rt-PA plus unfractionated heparin (UFH) to UFH alone, rt-PA at different doses, or rt-PA by different routes of administration in the treatment of DVT. Outcomes had to be described in terms of percent change in venographic patency for efficacy (>50% lysis) and in sufficient detail for complications (major and minor hemorrhages and other). The search strategy included searching electronic databases and contacting pharmaceutical agencies and content experts. Study quality was assessed using the Jadad scale. A threshold quality score was used to exclude trials.
  
  
  RESULTS
  Five studies met the following inclusion criteria: three comparing rt-PA plus UFH vs UFH alone (180 patients); one comparing high-dose vs low-dose rt-PA (32 patients); and one comparing systemic vs local administration of rt-PA (151 patients). In studies comparing rt-PA vs placebo, patients assigned to rt-PA were more likely to have > 50% lysis and complications (summary odds ratios [OR], 11.7; 95% confidence interval [CI], 2.61 to 52.5; and OR, 9.95; 95% CI, 2.21 to 44.7, respectively). Major and intracerebral hemorrhages were not significantly increased. One study comparing different doses demonstrated that high-dose and low-dose rt-PA were equally efficacious (OR, 0.88; 95% CI, 0.05 to 14.78). Local rt-PA was neither more efficacious nor riskier than systemic rt-PA.
  
  
  CONCLUSIONS
  This systematic review does not support routine use of rt-PA for DVT.
authors.affiliation: Division of General Internal Medicine, Ottawa Hospital, Civic Campus, University of Ottawa, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Forster
authors.forename: P
authors.initials: P
authors.lastname: Wells
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use; D002543:Cerebral Hemorrhage / Q000517:prevention & control; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D013300:Streptokinase / Q000627:therapeutic use; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D020246:Venous Thrombosis / Q000188:drug therapy*
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D006493:Heparin; D013300:Streptokinase; D010959:Tissue Plasminogen Activator