title: Safety and efficacy of oral factor-Xa inhibitors versus Vitamin K antagonist in patients with non-valvular atrial fibrillation: Meta-analysis of phase II and III randomized controlled trials.
abstract: BACKGROUND
  Aim of our study was to assess the safety and efficacy on factor-Xa inhibitors (FXIs) in patients with non-valvular atrial fibrillation (NVAF) as compared to Vitamin K antagonist (VKA).
  
  
  METHODS
  Phase II and III randomized controlled trials that reported clinical safety and efficacy of FXI in patients with NVAF were identified from MEDLINE, Embase, and Cochrane Central Register of Controlled Trials through December 10, 2015. The primary safety outcome of our study was composite of stroke and systemic embolic event. Secondary outcomes studied were individual endpoints of primary safety outcome, major bleeding, clinically relevant non-major bleed (CRNMB), and all-cause mortality.
  
  
  RESULTS
  We included 11 RCTs with a total of 59,164 participants, of which 34,231 patients received oral FXI and 24,933 patients were on VKA with a mean follow-up of 369days. There was a significant reduction in primary outcome with FXI compared to VKA, 1,112 (3.4%) versus 816 (3.6%) events, respectively (OR 0.82; 95% CI 0.68-0.99). Use of FXI significantly reduced major bleeding events compared to VKA, OR 0.74, 95% CI 0.58-0.96, test for heterogeneity (I(2)=74%). Incidence of CRNMB was not different between FXI and VKA groups, OR 0.84, 95% CI 0.68-1.04. There was a significant reduction in all-cause mortality in FXI group compared to VKA group, OR 0.88, 95% CI 0.83-0.94 with no significant heterogeneity.
  
  
  CONCLUSIONS
  Use of FXI was associated with a significant reduction in major bleeding events and all-cause mortality without increased risk of stroke or SEE compared to VKA.
authors.affiliation: Division of Cardiology, Lehigh Valley Health Network, Allentown, PA, United States. Electronic address: garg.jalaj@yahoo.com.
authors.forename: Jalaj
authors.initials: J
authors.lastname: Garg
authors.affiliation: Department of Medicine, Sinai Hospital of Baltimore, Johns Hopkins University, Baltimore, MD, United States.
authors.forename: Rahul
authors.initials: R
authors.lastname: Chaudhary
authors.affiliation: Department of Medicine, Division of Cardiology, Einstein Healthcare Network, Philadelphia, PA, United States.
authors.forename: Parasuram
authors.initials: P
authors.lastname: Krishnamoorthy
authors.affiliation: Helmsley Electrophysiology Center, Mount Sinai School of Medicine, New York, NY, United States.
authors.forename: Chandrasekar
authors.initials: C
authors.lastname: Palaniswamy
authors.affiliation: Division of Cardiology, Lehigh Valley Health Network, Allentown, PA, United States.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Shah
authors.affiliation: Division of Cardiology, Lehigh Valley Health Network, Allentown, PA, United States.
authors.forename: Babak
authors.initials: B
authors.lastname: Bozorgnia
authors.affiliation: Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin, TX, United States.
authors.forename: Andrea
authors.initials: A
authors.lastname: Natale
mesh_terms: D000284:Administration, Oral; D001281:Atrial Fibrillation / Q000188:drug therapy*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D065427:Factor Xa Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D065427:Factor Xa Inhibitors; D014812:Vitamin K
keywords: All-cause mortality; Atrial fibrillation; Bleeding; Factor X inhibitors; Stroke