title: Direct oral anticoagulants in the treatment of acute venous thromboembolism: a systematic review and meta-analysis.
abstract: BACKGROUND
  Acute venous thromboembolism (VTE) is a common disease associated to significant morbidity and mortality.
  
  
  METHODS
  We systematically reviewed and meta-analysed clinical outcomes with direct oral anticoagulants (DOAC: dabigatran, rivaroxaban, apixaban or edoxaban) for treatment of acute VTE. We used MEDLINE and CENTRAL, clinical trials registers, conference proceedings, and websites of regulatory agencies to identify randomised clinical trials of DOAC compared with conventional treatment [parenteral anticoagulant followed by a vitamin K antagonist (VKA)] for acute VTE. Two investigators independently extracted data. Relative risk of recurrent VTE, bleeding events, deaths and a net clinical endpoint (composite of recurrent VTE, major bleeding, and death) were estimated using a random effect meta-analysis (RevMan software).
  
  
  RESULTS
  Six trials including 27,127 patients were selected. The risk of recurrent VTE was similar with the DOAC and standard treatment (relative risk 0.91, 95% confidence interval 0.79 to 1.06). The DOAC reduced the risk of major bleeding in comparison with standard treatment (0.62, 0.45 to 0.85) (absolute risk difference, -0.6%; 95% confidence interval -1.0% to -0.3%), but there was heterogeneity across trials in the relative risk of bleeding. No between treatment differences were found in the relative risk of all-cause mortality (0.98, 0.84 to 1.14). The DOAC and conventional treatment differed on the net clinical endpoint (0.85, 0.75 to 0.97). Subgroup analyses in relevant subgroups (index pulmonary embolism, heparin lead-in, age, gender, renal function, presence of cancer), as well as sensitivity analyses, were consistent with the main analysis.
  
  
  CONCLUSIONS
  The DOAC seem as effective as, and probably safer than standard treatment of acute VTE. The relative efficacy and safety of the DOAC was consistent across a wide range of patients.
authors.affiliation: Division of Pharmacology and Clinical Evaluation, Medicines for Human Use, Spanish Agency for Medicines and Medical Devices (AEMPS), Madrid, Spain. Electronic address: agomezo@aemps.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gómez-Outes
authors.affiliation: Department of Clinical Pharmacology, Hospital Clínico San Carlos, Madrid, Spain; Department of Pharmacology, Universidad Complutense, Madrid, Spain.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Terleira-Fernández
authors.affiliation: Hematology Service, University Clinic of Navarra, Pamplona, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Lecumberri
authors.affiliation: Division of Pharmacology and Clinical Evaluation, Medicines for Human Use, Spanish Agency for Medicines and Medical Devices (AEMPS), Madrid, Spain.
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Suárez-Gea
authors.affiliation: Department of Clinical Pharmacology, Hospital Clínico San Carlos, Madrid, Spain; Department of Pharmacology, Universidad Complutense, Madrid, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Vargas-Castrillón
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069604:Dabigatran; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D009025:Morpholines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069552:Rivaroxaban; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D054556:Venous Thromboembolism / Q000188:drug therapy*; D015091:beta-Alanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D001562:Benzimidazoles; D009025:Morpholines; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D013844:Thiazoles; D013876:Thiophenes; D015091:beta-Alanine; C522181:apixaban; D000069552:Rivaroxaban; D000069604:Dabigatran; C552171:edoxaban
keywords: Apixaban; Dabigatran; Edoxaban; Rivaroxaban; Venous thromboembolism; Warfarin