title: Dabigatran and rivaroxaban for prevention of venous thromboembolism--systematic review and adjusted indirect comparison.
abstract: OBJECTIVE
  Dabigatran and rivaroxaban are new oral anticoagulants for thromboprophylaxis after elective orthopaedic surgery. We aimed to systematically compare their relative benefits and harms through meta-analysis, and adjusted indirect comparison.
  
  
  METHODS
  We searched PubMed, EMBASE, trial registries and regulatory documents through May 2009 for randomized controlled trials (RCTs) of dabigatran (150 and 220 mg daily) and rivaroxaban (10 mg daily) compared with enoxaparin (40-60 mg daily) in elective orthopaedic surgery. We used random effects meta-analysis to calculate pooled relative risks (RRs) and 95% confidence intervals (95% CI) for the outcomes of total venous thromboembolism, VTE (deep venous thrombosis, non-fatal pulmonary embolism and all-cause mortality), and haemorrhagic adverse events (major and clinically relevant non-major bleeds). Adjusted indirect comparison was used for the pooled RRs of dabigatran and rivaroxaban with enoxaparin as the common control.
  
  
  RESULTS
  Rivaroxaban was superior to enoxaparin for the prevention of venous thromoboembolism (RR 0.56, 95% CI 0.43-0.73, P<0.0001), with a trend for increased haemorrhage (RR 1.26, 95% CI 0.94-1.69, P=0.13). Dabigatran was not superior to enoxaparin for prevention of VTE (RR 1.12, 95% 0.97-1.29, P=0.12), and did not reduce haemorrhage risk (RR 1.10, 95% 0.90-1.35, P=0.32). Adjusted indirect comparison showed that rivaroxaban was superior to dabigatran in preventing VTE, RR 0.50 (95% CI 0.37-0.68), but with a slight trend towards increased haemorrhage RR 1.14 (95% CI 0.80-1.64).
  
  
  CONCLUSIONS
  Rivaroxaban may be more effective than dabigatran for prevention of VTE after elective orthopaedic surgery but might also slightly increase the risk of haemorrhage.
authors.affiliation: School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, UK. y.loke@uea.ac.uk
authors.forename: Y K
authors.initials: YK
authors.lastname: Loke
authors.forename: C S
authors.initials: CS
authors.lastname: Kwok
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D000991:Antithrombins / Q000009:adverse effects / Q000627:therapeutic use; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000069604:Dabigatran; D017984:Enoxaparin / Q000009:adverse effects / Q000627:therapeutic use; D065427:Factor Xa Inhibitors; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D009025:Morpholines / Q000009:adverse effects / Q000627:therapeutic use*; D019637:Orthopedic Procedures / Q000009:adverse effects*; D011183:Postoperative Complications / Q000517:prevention & control*; D011655:Pulmonary Embolism / Q000517:prevention & control; D000069552:Rivaroxaban; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D054556:Venous Thromboembolism / Q000517:prevention & control*; D020246:Venous Thrombosis / Q000517:prevention & control; D015091:beta-Alanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D001562:Benzimidazoles; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D015091:beta-Alanine; D000069552:Rivaroxaban; D000069604:Dabigatran