title: Net Clinical Benefit of Non-vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Phase III Atrial Fibrillation Trials.
abstract: OBJECTIVE
  The evaluation of the "net clinical benefit" allows an integrated assessment of both the anti-ischemic and the prohemorrhagic effects of non-vitamin K antagonist oral anticoagulants compared with warfarin, and—in the absence of direct comparisons—may inform clinical decisions. We estimated the net clinical benefit of non-vitamin K antagonist oral anticoagulants versus warfarin across the 4 phase III clinical trials performed in patients with atrial fibrillation.
  
  
  METHODS
  We considered various composites of the main ischemic and hemorrhagic events, estimating the rate ratio of all treatment groups versus warfarin for each composite outcome. Because the clinical relevance of the various ischemic or hemorrhagic events is not identical, we then attributed to each of them a weight, according to its impact on death, as derived from previous studies. We evaluated a weighed net clinical benefit of each non-vitamin K antagonist oral anticoagulant compared with warfarin in the 4 trials.
  
  
  RESULTS
  The composite outcome of ischemic + hemorrhagic stroke was reduced by dabigatran 150 mg and apixaban. The composite of disabling stroke + life-threatening bleeding was reduced by all non-vitamin K antagonist oral anticoagulants. The composite of ischemic stroke + systemic embolism + myocardial infarction + hemorrhagic stroke + major bleeding was reduced by apixaban and edoxaban at both doses. By attributing weights to these events according to their impact on mortality, all non-vitamin K antagonist oral anticoagulants featured a favorable net clinical benefit compared with warfarin, albeit to a quantitatively different extent.
  
  
  CONCLUSIONS
  The choice of the proper antithrombotic treatment in patients with atrial fibrillation has to consider the net clinical benefit of each drug. However, all non-vitamin K antagonist oral anticoagulants have a better efficacy/safety profile than warfarin in patients with atrial fibrillation.
authors.affiliation: Institute of Cardiology, Department of Neurosciences, Imaging and Clinical Sciences-Center of Excellence on Aging, "G. d'Annunzio" University, Chieti, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Renda
authors.affiliation: Laboratory of Biostatistics, Department of Experimental and Clinical Sciences, "G. d'Annunzio" University, Chieti, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: di Nicola
authors.affiliation: Institute of Cardiology, Department of Neurosciences, Imaging and Clinical Sciences-Center of Excellence on Aging, "G. d'Annunzio" University, Chieti, Italy; "G. Monasterio" Foundation, Pisa, Italy. Electronic address: rdecater@unich.it.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications*; D002545:Brain Ischemia / Q000517:prevention & control; D005260:Female; D006801:Humans; D020300:Intracranial Hemorrhages / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D012307:Risk Factors; D020521:Stroke / Q000517:prevention & control*; D013923:Thromboembolism / Q000517:prevention & control*; D016896:Treatment Outcome; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014859:Warfarin
keywords: Atrial fibrillation; Hemorrhagic risk; Net clinical benefit; Oral anticoagulants; Thromboembolic risk