title: Novel oral anticoagulants for the secondary prevention of cerebral ischemia: a network meta-analysis.
abstract: BACKGROUND
  Novel oral anticoagulants (NOACs) have shown to be both safe and effective for ischemic stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). We conducted a network meta-analysis (NMA) using published data from secondary prevention subgroups of different phase III randomized clinical trials (RCTs) comparing individual NOACs with warfarin.
  
  
  METHODS
  Eligible studies were identified by searching MEDLINE and SCOPUS and the Cochrane Central Register of Controlled Trials databases. First, we conducted a pairwise meta-analysis for each pairwise comparison, and then we performed NMA to combine direct and indirect evidence for any given pair of treatments. The comparative effects of all NOACs against warfarin were ranked with the surface under the cumulative ranking (SUCRA) curve for each outcome.
  
  
  RESULTS
  We identified four RCTs (including 15,240 patients) comparing individual NOACs (apixaban, dabigatran, rivaroxaban) with warfarin. Using indirect evidence, dabigatran was related to a significantly lower risk of hemorrhagic stroke compared with rivaroxaban [risk ratio (RR) 0.28; 95% confidence interval (CI) 0.11-0.75], while rivaroxaban was associated with a significantly lower risk of major gastrointestinal bleeding compared with dabigatran (RR 0.14; 95% CI 0.03-0.74). We also performed clustered ranking plot for the primary efficacy and safety endpoints to identify the treatment with the probably best benefit-to-risk ratio profile.
  
  
  CONCLUSIONS
  The three NOACs showed differences in terms of safety and efficacy for secondary stroke prevention in NVAF. Our findings can serve only as hypothesis generation and require independent confirmation in head-to-head RCTs, owing to the sparse available evidence and increased uncertainty in both indirect effect estimates and ranking of treatments.
authors: Department of Neurology, University of Ioannina School of Medicine, Ioannina, Greece Second Department of Neurology, 'Attikon University Hospital', School of Medicine, University of Athens, Athens, Greece.
authors: Aristeidis H
authors: AH
authors: Katsanos
authors: Department of Primary Education, University of Ioannina, Ioannina, Greece Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece.
authors: Dimitris
authors: D
authors: Mavridis
authors: Second Department of Cardiology, 'Attikon University Hospital', School of Medicine, University of Athens, Athens, Greece.
authors: John
authors: J
authors: Parissis
authors: Second Department of Cardiology, 'Attikon University Hospital', School of Medicine, University of Athens, Athens, Greece.
authors: Spyridon
authors: S
authors: Deftereos
authors: Second Department of Cardiology, 'Attikon University Hospital', School of Medicine, University of Athens, Athens, Greece.
authors: Alexandra
authors: A
authors: Frogoudaki
authors: Second Department of Cardiology, 'Attikon University Hospital', School of Medicine, University of Athens, Athens, Greece.
authors: Agathi-Rosa
authors: AR
authors: Vrettou
authors: Second Department of Cardiology, 'Attikon University Hospital', School of Medicine, University of Athens, Athens, Greece.
authors: Ignatios
authors: I
authors: Ikonomidis
authors: Second Department of Neurology, Attikon University Hospital, School of Medicine, University of Athens, Athens, Greece.
authors: Maria
authors: M
authors: Chondrogianni
authors: Second Department of Neurology, Attikon University Hospital, School of Medicine, University of Athens, Athens, Greece.
authors: Apostolos
authors: A
authors: Safouris
authors: Second Department of Neurology, Attikon University Hospital, School of Medicine, University of Athens, Athens, Greece.
authors: Angeliki
authors: A
authors: Filippatou
authors: Second Department of Neurology, Attikon University Hospital, School of Medicine, University of Athens, Athens, Greece.
authors: Konstantinos
authors: K
authors: Voumvourakis
authors: First Department of Neurology, 'Attikon University Hospital', School of Medicine, University of Athens, Athens, Greece.
authors: Nikos
authors: N
authors: Triantafyllou
authors: Department of Neurology, University of Patras, Patras, Greece.
authors: John
authors: J
authors: Ellul
authors: Second Department of Neurology, Aristotelian University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece.
authors: Theodore
authors: T
authors: Karapanayiotides
authors: Department of Neurology, University of Ioannina School of Medicine, Ioannina, Greece.
authors: Sotirios
authors: S
authors: Giannopoulos
authors: Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA Australian Catholic University, Sydney, Australia.
authors: Anne W
authors: AW
authors: Alexandrov
authors: Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA.
authors: Andrei V
authors: AV
authors: Alexandrov
authors: Second Department of Neurology, Attikon University Hospital, University of Athens, School of Medicine, Iras 39, Gerakas Attikis, Athens, 15344, Greece.
authors: Georgios
authors: G
authors: Tsivgoulis
keywords: apixaban; dabigatran; ischemic stroke; novel oral anticoagulant; rivaroxaban; transient ischemic attack