title: Safety and effectiveness of oral rivaroxaban versus standard anticoagulation for the treatment of symptomatic deep-vein thrombosis (XALIA): an international, prospective, non-interventional study.
abstract: BACKGROUND
  The efficacy and safety of the anticoagulant rivaroxaban for the treatment and secondary prevention of deep-vein thrombosis and pulmonary embolism has been shown in phase 3 trials. However, data about rivaroxaban use in routine clinical practice are needed.
  
  
  METHODS
  XA inhibition with rivaroxaban for Long-term and Initial Anticoagulation in venous thromboembolism (XALIA) was a multicentre, international, prospective, non-interventional study of patients with deep-vein thrombosis, done in hospitals and community care centres in 21 countries. The study investigated the safety and effectiveness of rivaroxaban compared with standard anticoagulation therapy (initial treatment with unfractionated heparin, low-molecular-weight heparin, or fondaparinux, usually overlapping with and followed by a vitamin K antagonist) for at least 3 months. Eligible patients were adults (aged ≥18 years) with an objectively confirmed diagnosis of deep-vein thrombosis, and an indication to receive anticoagulation treatment for at least 3 months. Following approval of rivaroxaban for the pulmonary embolism indication, patients with deep-vein thrombosis and concomitant pulmonary embolism were also eligible; however, those with isolated pulmonary embolism were not included. Type, dose, and duration of therapy for each patient were at the physician's discretion. The primary effectiveness and safety outcomes were major bleeding, recurrent venous thromboembolism, and all-cause mortality. Propensity score-adjusted analyses were done to account for potential imbalances between groups. This study is registered with ClinicalTrials.gov, number NCT01619007.
  
  
  RESULTS
  Between June 26, 2012, and March 31, 2014, 5142 patients were enrolled. The safety population (all patients who received at least one dose of the anticoagulant of interest) comprised 2619 patients in the rivaroxaban group and 2149 in the standard anticoagulant therapy group. Patients in the rivaroxaban group were younger and fewer had active cancer or concomitant pulmonary embolism than those in the standard anticoagulation group. In the propensity score-adjusted population, the frequency of major bleeding was 0·8% (19/2505) in the rivaroxaban group and 2·1% (43/2010) in the standard anticoagulation group, with a propensity score-adjusted hazard ratio (HR) of 0·77 (95% CI 0·40-1·50); p=0·44. The frequency of recurrent venous thromboembolism was 1·4% (36/2505) in the rivaroxaban group and 2·3% (47/2010) in the standard anticoagulation group (propensity score-adjusted HR 0·91 [95% CI 0·54-1·54], p=0·72). The all-cause mortality frequency was 0·4% (11/2505) in the rivaroxaban group and 3·4% (69/2010) in the standard anticoagulation group (propensity score-adjusted HR 0·51 [95% CI 0·24-1·07], p=0·074). The incidence of treatment-emergent adverse events in the safety population was similar between the two groups (944 [36·0%] of 2619 in the rivaroxaban group vs 805 [37·5%] of 2149 in the standard anticoagulation group).
  
  
  CONCLUSIONS
  In routine clinical practice, rivaroxaban-treated patients had a lower risk profile at baseline than those treated with standard anticoagulation. Propensity score-adjusted results confirm that rivaroxaban is a safe and effective alternative to standard anticoagulation therapy in a broad range of patients. Rates of major bleeding and recurrent venous thromboembolism were low in rivaroxaban-treated patients and consistent with phase 3 findings.
  
  
  BACKGROUND
  Bayer HealthCare Pharmaceuticals and Janssen Research & Development, LLC.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy. Electronic address: walter.ageno@uninsubria.it.
authors.forename: Walter
authors.initials: W
authors.lastname: Ageno
authors.affiliation: CESP-Center for Public Health Research, University of Milan Bicocca, Milan, Italy.
authors.forename: Lorenzo G
authors.initials: LG
authors.lastname: Mantovani
authors.affiliation: Vascular Centre, Munich, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Haas
authors.affiliation: Institute of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Reinhold
authors.initials: R
authors.lastname: Kreutz
authors.affiliation: Bayer Vital GmbH, Leverkusen, Germany.
authors.forename: Danja
authors.initials: D
authors.lastname: Monje
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Schneider
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: van Eickels
authors.affiliation: Bayer Pharma AG, Wuppertal, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Gebel
authors.affiliation: Stat-Epi Associates Inc, Ponte Vedra Beach, FL, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Zell
authors.affiliation: Department of Medicine, Hamilton Health Sciences, General Division, Hamilton, ON, Canada.
authors.forename: Alexander G G
authors.initials: AG
authors.lastname: Turpie
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D005260:Female; D000077425:Fondaparinux; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011134:Polysaccharides / Q000627:therapeutic use; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000188:drug therapy*; D000069552:Rivaroxaban / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000139:chemically induced; D020246:Venous Thrombosis / Q000188:drug therapy*
chemical_list: D000925:Anticoagulants; D011134:Polysaccharides; D006493:Heparin; D000069552:Rivaroxaban; D000077425:Fondaparinux