title: Sex related differences in patients with acute venous thromboembolism treated with new oral anticoagulants. A meta-analysis of the interventional trials.
abstract: BACKGROUND
  Gender differences have been reported in patients with acute VTE treated with antithrombotic drugs.
  
  
  OBJECTIVE
  To address the relationship between gender and new oral anticoagulants (NOACs), we performed a meta-analysis to evaluate the incidence of recurrent VTE and major plus clinically relevant non-major bleedings in males and females, with acute VTE, treated with NOACs over the treatment period.
  
  
  METHODS
  Systematic review and meta-analysis of double blind randomized controlled trials (RCTs).
  
  
  METHODS
  MEDLINE, Cochrane Library of Clinical Trials (up to September 2015).
  
  
  METHODS
  RCTs that compared the beneficial and harmful effects of NOAC drugs (apixaban, dabigatran, edoxaban and rivaroxaban).
  
  
  METHODS
  Three authors abstracted data. Study-specific risk ratios (RR) were combined using random-effects model.
  
  
  RESULTS
  Nine studies including 16,372 patients were selected. No significant difference for the incidence of recurrent VTE was found between men and women. Compared to men, women had a higher incidence of major bleedings plus clinically relevant minor bleedings (5.3% and 7.9% respectively; RR: 0.635; 95% CI: 0.54-0.74; p<0.001). The subgroup analysis showed a significant gender difference in incidence of major bleedings and clinically relevant minor bleedings only for Edoxaban (RR: 0.52; 95% CI: 0.42-0.64; p<0.001).
  
  
  CONCLUSIONS
  This meta-analysis showed, compared to men, a higher risk of bleeding in women with acute VTE treated with NOACs. Future trials should evaluate the effect of gender on bleeding in patients with acute VTE treated with NOACs.
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy. Electronic address: lorenzo.loffredo@uniroma1.it.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Loffredo
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Violi
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
authors.forename: Ludovica
authors.initials: L
authors.lastname: Perri
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D000069604:Dabigatran / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D000069552:Rivaroxaban / Q000008:administration & dosage / Q000009:adverse effects; D012727:Sex Characteristics; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000188:drug therapy*
chemical_list: D000925:Anticoagulants; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D013844:Thiazoles; C522181:apixaban; D000069552:Rivaroxaban; D000069604:Dabigatran; C552171:edoxaban
keywords: Direct oral anticoagulants; Gender; New oral anticoagulants; Venous thromboembolism