title: Clinical and safety outcomes associated with treatment of acute venous thromboembolism: a systematic review and meta-analysis.
abstract: OBJECTIVE
  Many anticoagulant strategies are available for the treatment of acute venous thromboembolism, yet little guidance exists regarding which drug is most effective and safe.
  
  
  OBJECTIVE
  To summarize and compare the efficacy and safety outcomes associated with 8 anticoagulation options (unfractionated heparin [UFH], low-molecular-weight heparin [LMWH], or fondaparinux in combination with vitamin K antagonists); LMWH with dabigatran or edoxaban; rivaroxaban; apixaban; and LMWH alone) for treatment of venous thromboembolism.
  
  
  METHODS
  A systematic literature search was conducted using MEDLINE, EMBASE, and the evidence-based medicine reviews from inception through February 28, 2014.
  
  
  METHODS
  Eligible studies were randomized trials reporting rates of recurrent venous thromboembolism and major bleeding in patients with acute venous thromboembolism. Of the 1197 studies identified, 45 trials including 44,989 patients were included in the analyses.
  
  
  METHODS
  Two reviewers independently extracted trial-level data including number of patients, duration of follow-up, and outcomes. The data were pooled using network meta-analysis.
  
  
  METHODS
  The primary clinical and safety outcomes were recurrent venous thromboembolism and major bleeding, respectively.
  
  
  RESULTS
  Compared with the LMWH-vitamin K antagonist combination, a treatment strategy using the UFH-vitamin K antagonist combination was associated with an increased risk of recurrent venous thromboembolism (hazard ratio [HR], 1.42; 95% credible interval [CrI], 1.15-1.79). The proportion of patients experiencing recurrent venous thromboembolism during 3 months of treatment were 1.84% (95% CrI, 1.33%-2.51%) for the UFH-vitamin K antagonist combination and 1.30% (95% CrI, 1.02%-1.62%) for the LMWH-vitamin K antagonist combination. Rivaroxaban (HR, 0.55; 95% CrI, 0.35-0.89) and apixaban (HR, 0.31; 95% CrI, 0.15-0.62) were associated with a lower risk of bleeding than was the LMWH-vitamin K antagonist combination, with a lower proportion of patients experiencing a major bleeding event during 3 months of anticoagulation: 0.49% (95% CrI, 0.29%-0.85%) for rivaroxaban, 0.28% (95% CrI, 0.14%-0.50%) for apixaban, and 0.89% (95% CrI, 0.66%-1.16%) for the LMWH-vitamin K antagonist combination.
  
  
  CONCLUSIONS
  Using meta-analytic pooling, there were no statistically significant differences for efficacy and safety associated with most treatment strategies used to treat acute venous thromboembolism compared with the LMWH-vitamin K antagonist combination. However, findings suggest that the UFH-vitamin K antagonist combination is associated with the least effective strategy and that rivaroxaban and apixaban may be associated with the lowest risk for bleeding.
authors.affiliation: Department of Medicine, the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Lana A
authors.initials: LA
authors.lastname: Castellucci
authors.affiliation: Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Chris
authors.initials: C
authors.lastname: Cameron
authors.affiliation: Department of Medicine, the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Grégoire
authors.initials: G
authors.lastname: Le Gal
authors.affiliation: Department of Medicine, the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Rodger
authors.affiliation: Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Doug
authors.initials: D
authors.lastname: Coyle
authors.affiliation: Department of Medicine, the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Wells
authors.affiliation: Canadian Agency for Drugs and Technologies in Health, Ottawa, Ontario, Canada.
authors.forename: Tammy
authors.initials: T
authors.lastname: Clifford
authors.affiliation: Department of Medicine, the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Esteban
authors.initials: E
authors.lastname: Gandara
authors.affiliation: Ottawa Heart Institute, Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Wells
authors.affiliation: Department of Medicine, the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Carrier
mesh_terms: D000208:Acute Disease; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D012306:Risk; D054556:Venous Thromboembolism / Q000188:drug therapy*
chemical_list: D000925:Anticoagulants