title: Risk of major bleeding in different indications for new oral anticoagulants: insights from a meta-analysis of approved dosages from 50 randomized trials.
abstract: BACKGROUND
  A meta-analysis was performed to evaluate the risk of major bleeding with the use of New Oral Anticoagulants (NOACs).
  
  
  METHODS
  Randomized controlled trials (RCTs) comparing NOACs (rivaroxaban, dabigatran, apixaban, edoxaban and darexaban) with comparators were selected.
  
  
  RESULTS
  Fifty trials included 155,537 patients. Pooled analysis of all NOACs for all indications together demonstrated no significant difference between NOACs and comparators for risk of major bleeding (odds ratio [OR] 0.93, 95% CI 0.79-1.09). Pooled analysis also showed that NOACs caused significantly less major bleeding compared to vitamin K antagonists (VKA) (0.77, 0.64-0.91). The analysis for individual NOACs showed risk of major bleeding were not different with rivaroxaban, apixaban or dabigatran compared to pharmacologically active comparators or VKA. Indication specific analysis showed that NOACs were associated with significantly higher major bleeding after hip surgery (1.43, 1.02-1.99), in patients with acute coronary syndrome (ACS), (compared against placebo) (2.89, 2.01-4.14), and for medically ill patients (2.79, 1.69-4.60). For the treatment of acute venous thromboembolism (VTE) or pulmonary embolism (PE), NOACs were associated with significantly less bleeding (0.63, 0.44-0.90). No significant difference was found between NOACs and comparators in treatment of atrial fibrillation and for extended treatment of VTE.
  
  
  CONCLUSIONS
  Risk of major bleeding with new oral anticoagulants varies with their indication for use. New agents may be associated with comparatively less major bleeding compared to VKA. NOAC may increase the risk of major bleeding after hip surgery, ACS and acute medically ill patients; but may be associated with less bleeding in treatment of acute VTE/PE.
authors.affiliation: Texas Tech University Health Sciences Center, El Paso, TX, United States. Electronic address: parthasardarmd@gmail.com.
authors.forename: Partha
authors.initials: P
authors.lastname: Sardar
authors.affiliation: St Luke's-Roosevelt Hospital of the Mount Sinai Health System, New York, NY, United States.
authors.forename: Saurav
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: John Ochsner Heart and Vascular Institute, Ochsner Clinical School, The University of Queensland School of Medicine, New Orleans, LA, United States.
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Lavie
authors.affiliation: Cardiovascular Division, Hospital of the University of Pennsylvania, Philadelphia, PA, United States.
authors.forename: Jay S
authors.initials: JS
authors.lastname: Giri
authors.affiliation: Columbia University of Physicians and Surgeons, New York, NY, United States.
authors.forename: Joydeep
authors.initials: J
authors.lastname: Ghosh
authors.affiliation: Texas Tech University Health Sciences Center, El Paso, TX, United States.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Mukherjee
authors.affiliation: University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom.
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
mesh_terms: D000284:Administration, Oral; D000991:Antithrombins / Q000008:administration & dosage* / Q000009:adverse effects*; D001381:Azepines / Q000008:administration & dosage / Q000009:adverse effects; D001549:Benzamides / Q000008:administration & dosage / Q000009:adverse effects; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects; D000069604:Dabigatran; D065427:Factor Xa Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D009025:Morpholines / Q000008:administration & dosage / Q000009:adverse effects; 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; D012306:Risk; D000069552:Rivaroxaban; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects; D015091:beta-Alanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D000991:Antithrombins; D001381:Azepines; D001549:Benzamides; D001562:Benzimidazoles; D065427:Factor Xa Inhibitors; D009025:Morpholines; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D013844:Thiazoles; D013876:Thiophenes; D015091:beta-Alanine; C522181:apixaban; D000069552:Rivaroxaban; D000069604:Dabigatran; C569750:darexaban; C552171:edoxaban
keywords: Apixaban; Bleeding; Dabigatran; Meta-analysis; New oral anticoagulants; Rivaroxaban