title: Comparative effectiveness of warfarin and new oral anticoagulants for the management of atrial fibrillation and venous thromboembolism: a systematic review.
abstract: BACKGROUND
  New oral anticoagulants (NOACs), including direct thrombin inhibitors (DTIs) and factor Xa (FXa) inhibitors, are emerging alternatives for prophylaxis and treatment of atrial fibrillation (AF) and venous thromboembolism (VTE).
  
  
  OBJECTIVE
  To compare the benefits and harms of NOACs versus warfarin for AF and VTE.
  
  
  METHODS
  MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from January 2001 through July 2012; U.S. Food and Drug Administration (FDA) database for adverse event reports.
  
  
  METHODS
  English-language, randomized, controlled trials (RCTs) comparing NOACs with warfarin for management of AF or VTE and observational studies and FDA reports on adverse effects.
  
  
  METHODS
  Two independent reviewers abstracted data and rated study quality and strength of evidence.
  
  
  RESULTS
  Six good-quality RCTs compared NOACs (2 DTI studies, 4 FXa inhibitor studies) with warfarin. In AF, NOACs decreased all-cause mortality (risk ratio [RR], 0.88 [95% CI, 0.82 to 0.96]); in VTE, NOACs did not differ for mortality or VTE outcomes. Across indications, adverse effects of NOACs compared with warfarin were fatal bleeding (RR, 0.60 [CI, 0.46 to 0.77]), major bleeding (RR, 0.80 [CI, 0.63 to 1.01]), gastrointestinal bleeding (RR, 1.30 [CI, 0.97 to 1.73]), and discontinuation due to adverse events (RR, 1.23 [CI, 1.05 to 1.44]). Subgroup analyses suggest a higher risk for myocardial infarction with DTIs than with FXa inhibitors. Bleeding risk for NOACs may be increased in persons older than 75 years or those receiving warfarin who have good control.
  
  
  CONCLUSIONS
  There were no head-to-head comparisons of NOACs and limited data on harms.
  
  
  CONCLUSIONS
  New oral anticoagulants are a viable option for patients receiving long-term anticoagulation. Treatment benefits compared with warfarin are small and vary depending on the control achieved by warfarin treatment.
  
  
  BACKGROUND
  Department of Veterans Affairs.
authors.affiliation: Duke University Medical Center, Department of Medicine, Box 3939, Durham, NC 27710, USA.
authors.forename: Soheir S
authors.initials: SS
authors.lastname: Adam
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: McDuffie
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Ortel
authors.forename: John W
authors.initials: JW
authors.lastname: Williams
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D000991:Antithrombins / Q000009:adverse effects / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000517:prevention & control; D057186:Comparative Effectiveness Research; D065427:Factor Xa Inhibitors; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D055502:Secondary Prevention; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000188:drug therapy* / Q000517:prevention & control; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D065427:Factor Xa Inhibitors; D014859:Warfarin