title: Comparative effectiveness of novel oral anticoagulants for atrial fibrillation: evidence from pair-wise and warfarin-controlled network meta-analyses.
abstract: BACKGROUND
  Novel oral anticoagulants have been tested against warfarin for atrial fibrillation, yet no direct comparison is available. We thus aimed to perform pair-wise (direct) and warfarin-adjusted network (i.e. indirect) meta-analyses of novel oral anticoagulants for atrial fibrillation.
  
  
  METHODS
  Databases were searched for randomized warfarin-controlled trials of novel anticoagulants for non-valvular atrial fibrillation. The primary end-point was long-term stroke/systemic embolism. Odds ratios (95% intervals) were computed with RevMan and WinBUGS.
  
  
  RESULTS
  Seven trials (52701 patients) were included, focusing on apixaban, dabigatran, edoxaban and rivaroxaban. Pair-wise meta-analysis showed that after a weighted average of 23 months these novel anticoagulants lead to significant reductions in the risk of stroke/systemic embolism (odds ratio=0.81 [0.71-0.92], I2=23%) and all cause death (odds ratio=0.88 [0.82-0.95], I2=0%) in comparison to warfarin. Network meta-analysis showed that apixaban and dabigatran proved similarly superior to warfarin in preventing stroke/systemic embolism (odds ratio=0.78 [0.62-0.96] for apixaban vs warfarin; odds ratio=0.66 [0.52-0.84] for high-dose dabigatran vs warfarin; odds ratio for apixaban vs high-dose dabigatran=1.17 [0.85-1.63]), but apixaban was associated with fewer major bleedings (odds ratio=0.73 [0.57-0.93]) and drug discontinuations (odds ratio=0.64 [0.52-0.78]) than dabigatran. Rivaroxaban did not reduce stroke/systemic embolism (odds ratio=0.87 [0.71-1.07]) or major bleedings in comparison to warfarin (odds ratio=0.87 [0.71-1.07]) and was associated with more major bleedings in comparison to apixaban (odds ratio=1.52 [1.19-1.92]). Data for edoxaban were inconclusive.
  
  
  CONCLUSIONS
  Novel oral anticoagulants appear as a very promising treatment option for atrial fibrillation.
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Biondi-Zoccai
authors.forename: V
authors.initials: V
authors.lastname: Malavasi
authors.forename: F
authors.initials: F
authors.lastname: D'Ascenzo
authors.forename: A
authors.initials: A
authors.lastname: Abbate
authors.forename: P
authors.initials: P
authors.lastname: Agostoni
authors.forename: M
authors.initials: M
authors.lastname: Lotrionte
authors.forename: D
authors.initials: D
authors.lastname: Castagno
authors.forename: B
authors.initials: B
authors.lastname: Van Tassell
authors.forename: E
authors.initials: E
authors.lastname: Casali
authors.forename: M
authors.initials: M
authors.lastname: Marietta
authors.forename: M G
authors.initials: MG
authors.lastname: Modena
authors.forename: K A
authors.initials: KA
authors.lastname: Ellenbogen
authors.forename: G
authors.initials: G
authors.lastname: Frati
keywords: apixaban; atrial fibrillation; dabigatran; meta-analysis; rivaroxaban; systematic review; warfarin