title: Testing the therapeutic equivalence of novel oral anticoagulants for thromboprophylaxis in orthopedic surgery and for prevention of stroke in atrial fibrillation.
abstract: BACKGROUND
  In studying the comparative effectiveness of novel oral anticoagulants (NOACs) in orthopedic surgery and in non-valvular atrial fibrillation, previous meta-analyses have found no proof of difference in head-to-head indirect comparisons between individual agents. However, the question of their therapeutic equivalence remains unanswered.
  
  
  OBJECTIVE
  The objective of this analysis was to test the equivalence of three NOACs (dabigatran, rivaroxaban, apixaban) in orthopedic surgery and four NOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) in non-valvular atrial fibrillation.
  
  
  METHODS
  Standard pairwise meta-analysis and network meta-analysis for indirect comparisons were combined with equivalence testing. The endpoint was venous thromboembolism in orthopedic surgery and a composite of stroke or systemic embolism in atrial fibrillation. Comparisons were expressed as risk difference (RD). Margins for equivalence testing were derived from the original trials.
  
  
  RESULTS
  Our results indicate that rivaroxaban and apixaban (but not dabigatran) are equivalent for thromboprophylaxis in orthopedic surgery. In atrial fibrillation, all the four NOACs we tested were found to meet the criterion of therapeutic equivalence. Some concern, however, is raised by some findings focused on adverse events of these agents, in which the equivalence was not proven in all analyses.
  
  
  CONCLUSIONS
  Regardless of clinical implications, our results can be the basis to develop local acquisition tenderings on NOACS. In Italy, a new law has been issued according to which equivalence analyses have become a mandatory prerequisite for local tenderings.
authors.forename: Andrea
authors.initials: A
authors.lastname: Messori
authors.forename: Valeria
authors.initials: V
authors.lastname: Fadda
authors.forename: Dario
authors.initials: D
authors.lastname: Maratea
authors.forename: Sabrina
authors.initials: S
authors.lastname: Trippoli
authors.forename: Claudio
authors.initials: C
authors.lastname: Marinai
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D001562:Benzimidazoles / Q000008:administration & dosage; D001777:Blood Coagulation / Q000187:drug effects*; D000069604:Dabigatran; D006801:Humans; D009025:Morpholines / Q000008:administration & dosage; D019637:Orthopedic Procedures / Q000009:adverse effects*; D061214:Patient Safety; D011720:Pyrazoles / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D011728:Pyridones / Q000008:administration & dosage; D018570:Risk Assessment; D000069552:Rivaroxaban; D020521:Stroke / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D013810:Therapeutic Equivalency; D013844:Thiazoles / Q000008:administration & dosage; D013876:Thiophenes / Q000008:administration & dosage; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D015091:beta-Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives
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