title: Comparison of Approaches for Stroke Prophylaxis in Patients with Non-Valvular Atrial Fibrillation: Network Meta-Analyses of Randomized Controlled Trials.
abstract: BACKGROUND
  Multiple novel oral anticoagulants and left atrial appendage closure devices (WATCHMAN) have been tested against dose-adjusted vitamin K antagonists in randomized controlled trials for stroke prophylaxis in non-valvular atrial fibrillation. No direct comparisons of these strategies are available from randomized controlled trials. We conducted the current analyses by combining efficacy and safety characteristics of all FDA approved stroke prophylaxis treatment strategies for patients with non-valvular atrial fibrillation.
  
  
  METHODS
  We searched SCOPUS from 1945 till October 2015 for randomized controlled trials comparing these strategies and reporting efficacy and safety outcomes. Six randomized controlled trials were identified and included in the final analyses and review. We followed PRISMA guidelines for network meta-analyses while reporting the current analyses. We collected data on ischemic stroke, major bleeding, and the composite primary safety endpoint as defined by various randomized controlled trials. Network meta-analyses were conducted using consistency and inconsistency models for efficacy and safety outcomes. Surface under the cumulative ranking curve were then utilized to cluster rank these treatments for safety and efficacy.
  
  
  RESULTS
  Six randomized controlled trials with 59,627 patients comparing six treatment strategies were eligible for the analyses. All prophylaxis strategies had comparable rates of ischemic stroke. Apixaban was associated with the least number of primary safety endpoint events as compared with all other treatments. In the cluster analyses assessing safety and efficacy, apixaban, edoxaban and dabigatran ranked best followed by vitamin K antagonists and rivaroxaban, whereas the WATCHMAN left atrial appendage closure device ranked last.
  
  
  CONCLUSIONS
  Dose-adjusted vitamin K antagonists, novel oral anticoagulants, and the WATCHMAN left atrial appendage closure devices are equally efficacious for ischemic stroke prevention but these treatments have different safety profiles. More randomized controlled trials are needed to directly compare these strategies.
authors.affiliation: Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States of America.|Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Navkaranbir S
authors.initials: NS
authors.lastname: Bajaj
authors.affiliation: Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN, United States of America.|Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Rajat
authors.identifier: http://orcid.org/0000-0002-8982-0595
authors.initials: R
authors.lastname: Kalra
authors.affiliation: Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Nirav
authors.initials: N
authors.lastname: Patel
authors.affiliation: Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Taimoor
authors.initials: T
authors.lastname: Hashim
authors.affiliation: Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Hemant
authors.initials: H
authors.lastname: Godara
authors.affiliation: Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Sameer
authors.initials: S
authors.lastname: Ather
authors.affiliation: Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Garima
authors.initials: G
authors.lastname: Arora
authors.affiliation: Division of Cardiovascular Medicine, University of Utah School of Medicine, Salt Lake City, UT, United States of America.
authors.forename: Tilak
authors.initials: T
authors.lastname: Pasala
authors.affiliation: Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Whitfield
authors.affiliation: Division of Cardiac Surgery, Department of Surgery, Alfred Hospital and Monash University, Melbourne, Australia.
authors.forename: David C
authors.initials: DC
authors.lastname: McGiffin
authors.affiliation: Division of Cardiology, Baptist Princeton, Birmingham, Alabama, United States of America.
authors.forename: Mustafa I
authors.initials: MI
authors.lastname: Ahmed
authors.affiliation: Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Lloyd
authors.affiliation: Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Nita A
authors.initials: NA
authors.lastname: Limdi
authors.affiliation: Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Arora
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000627:therapeutic use; D020517:Atrial Appendage / Q000601:surgery*; D001281:Atrial Fibrillation / Q000150:complications*; D005260:Female; D006801:Humans; D008297:Male; D016032:Randomized Controlled Trials as Topic; D055989:Septal Occluder Device; D020521:Stroke / Q000517:prevention & control*; D016896:Treatment Outcome; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D014812:Vitamin K