title: Gender Difference in Efficacy and Safety of Nonvitamin K Antagonist Oral Anticoagulants in Patients with Nonvalvular Atrial Fibrillation or Venous Thromboembolism: A Systematic Review and a Meta-Analysis of the Literature.
abstract: BACKGROUND
  Limited information exists on gender-related differences in the safety and efficacy of non-vitamin K antagonist oral anticoagulants (NOACs).
  
  
  OBJECTIVE
  To assess the safety and efficacy of direct oral anticoagulants (DOACs)/NOACs in men and women pooling data from randomized controlled trials on the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF) and on the acute and extended treatment of venous thromboembolism (VTE).
  
  
  METHODS
  MEDLINE and EMBASE databases were searched up to June 2014. The efficacy outcome was defined as the prevention of stroke and systemic embolism (AF studies), or as the prevention of recurrent VTE or VTE-related death (VTE studies). The safety outcome was defined as the occurrence of major and/or clinically relevant non-major bleeding. Differences in the efficacy and safety outcomes were expressed as risk ratio (RR) with pertinent 95% confidence intervals (95% CI).
  
  
  RESULTS
  A total of 13 studies (> 100,000 patients) were included. DOACs appeared to have a similar efficacy and safety compared with vitamin K antagonists in female and male patients treated for nonvalvular AF and acute VTE. In the extended treatment of VTE NOACs had a RR of bleeding of 4.97 (95% CI 1.06, 23.41) in males and 1.33 (95% CI 0.63, 2.83) in females compared with placebo (subgroup difference chi-square test: 2.25, p = 0.13).
  
  
  CONCLUSIONS
  No gender-related difference in the efficacy and safety of NOACs in patients with AF or acute VTE was found. A trend toward an increased risk of bleeding in male patients as compared with female patients was detected in the extended treatment of VTE.
authors.affiliation: Department of Clinical and Experimental Medicine, Insubria University, Varese, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Dentali
authors.affiliation: Department of Clinical and Experimental Medicine, Insubria University, Varese, Italy.
authors.forename: Anna Paola
authors.initials: AP
authors.lastname: Sironi
authors.affiliation: Department of Cardiology, Tradate Hospital, Tradate, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Gianni
authors.affiliation: Department of Internal Medicine, Ligurian East Hospital, La Spezia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Orlandini
authors.affiliation: Department of Clinical and Experimental Medicine, Insubria University, Varese, Italy.
authors.forename: Luigina
authors.initials: L
authors.lastname: Guasti
authors.affiliation: Department of Clinical and Experimental Medicine, Insubria University, Varese, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Grandi
authors.affiliation: Department of Transfusion Medicine and Hematology, Azienda Ospedaliera Carlo Poma, Mantova, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Franchini
authors.affiliation: Department of Clinical and Experimental Medicine, Insubria University, Varese, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Ageno
authors.affiliation: Department of Clinical and Experimental Medicine, Insubria University, Varese, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Squizzato
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D016032:Randomized Controlled Trials as Topic; D012727:Sex Characteristics; D054556:Venous Thromboembolism / Q000188:drug therapy*; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D014812:Vitamin K