title: Efficacy and safety outcomes of oral anticoagulants and antiplatelet drugs in the secondary prevention of venous thromboembolism: systematic review and network meta-analysis.
abstract: OBJECTIVE
  To summarise and compare the efficacy and safety of various oral anticoagulants (dabigatran, rivaroxaban, apixaban, and vitamin K antagonists) and antiplatelet agents (acetylsalicylic acid) for the secondary prevention of venous thromboembolism.
  
  
  METHODS
  Systematic review and network meta-analysis.
  
  
  METHODS
  Literature search using Medline (1950 to present), Embase (1980 to present), and the Cochrane Register of Controlled Trials using the OVID interface. Publications from potentially relevant journals were also searched by hand.
  
  
  METHODS
  Randomised controlled trials of patients receiving anticoagulants, antiplatelet drugs, or placebo or observation for secondary prevention of venous thromboembolism. Selected outcomes were rates of recurrent venous thromboembolism and major bleeding. Two reviewers independently extracted data onto standardised forms.
  
  
  RESULTS
  12 articles met our inclusion criteria, with 11,999 patients evaluated for efficacy and 12,167 for safety. All treatments reduced the risk of recurrent venous thromboembolism. Compared with placebo or observation, vitamin K antagonists at a standard adjusted dose (target international normalised ratio 2.0-3.0) showed the highest risk difference (odds ratio 0.07; 95% credible interval 0.03 to 0.15) and acetylsalicylic acid showed the lowest risk difference (0.65; 0.39 to 1.03). Risk of major bleeding was higher with a standard adjusted dose of vitamin K antagonists (5.24; 1.78 to 18.25) than with placebo or observation. Fatal recurrent venous thromboembolism and fatal bleeding were rare. Detailed subgroup and individual patient level data were not available.
  
  
  CONCLUSIONS
  All oral anticoagulants and antiplatelet agents investigated in this analysis were associated with a reduced recurrence of venous thromboembolism compared with placebo or observation, although acetylsalicylic acid was associated with the lowest risk reduction. Vitamin K antagonists given at a standard adjusted dose was associated with the greatest risk reduction in recurrent venous thromboembolism, but also the greatest risk of major bleeding.
authors.affiliation: Thrombosis Program, Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, ON, Canada K1H 8L6.
authors.forename: Lana A
authors.initials: LA
authors.lastname: Castellucci
authors.forename: Chris
authors.initials: C
authors.lastname: Cameron
authors.forename: Grégoire
authors.initials: G
authors.lastname: Le Gal
authors.forename: Marc A
authors.initials: MA
authors.lastname: Rodger
authors.forename: Doug
authors.initials: D
authors.lastname: Coyle
authors.forename: Philip S
authors.initials: PS
authors.lastname: Wells
authors.forename: Tammy
authors.initials: T
authors.lastname: Clifford
authors.forename: Esteban
authors.initials: E
authors.lastname: Gandara
authors.forename: George
authors.initials: G
authors.lastname: Wells
authors.forename: Marc
authors.initials: M
authors.lastname: Carrier
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use; D000069604:Dabigatran; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D009025:Morpholines / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use; D011728:Pyridones / Q000627:therapeutic use; D012008:Recurrence; D000069552:Rivaroxaban; D013876:Thiophenes / Q000627:therapeutic use; D054556:Venous Thromboembolism / Q000517:prevention & control*; D014812:Vitamin K / Q000037:antagonists & inhibitors; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D001562:Benzimidazoles; D009025:Morpholines; D010975:Platelet Aggregation Inhibitors; D011720:Pyrazoles; D011728:Pyridones; D013876:Thiophenes; D015091:beta-Alanine; D014812:Vitamin K; C522181:apixaban; D000069552:Rivaroxaban; D000069604:Dabigatran; D001241:Aspirin