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Horizontal vs. vertical dose reduction of direct oral anticoagulants in patients with non-valvular atrial fibrillation: definition and implications for practice

  • Andrea Rubboli
    Correspondence
    Corresponding author at: Department of Cardiovascular Diseases - AUSL Romagna, Division of Cardiology, Ospedale S. Maria delle Croci, Viale Randi 5, 48121 Ravenna, Italy.
    Affiliations
    Department of Cardiovascular Diseases - AUSL Romagna, Division of Cardiology, Ospedale S. Maria delle Croci, Ravenna, Italy
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Published:January 19, 2019DOI:https://doi.org/10.1016/j.ejim.2019.01.005
      Post-marketing surveillance is being showing a widespread use of the lower doses of direct oral anticoagulants (DOACs), namely dabigatran 110 mg, rivaroxaban 15 mg, apixaban 2.5 mg, and edoxaban 30 mg, for the prevention of stroke/systemic embolism in patients with non-valvular atrial fibrillation (NVAF) [
      • Steinberg B.A.
      • Shrader P.
      • Pieper K.
      • Thomas L.
      • Allen L.A.
      • Ansell J.
      • et al.
      Outcomes registry for better informed treatment of atrial fibrillation (ORBIT-AF) II investigators. Frequency and outcomes of reduced dose non-vitamin K antagonist anticoagulants: results from ORBIT-AF II (the outcomes registry for better informed treatment of atrial fibrillation II).
      ]. Use of the lower doses has been reported inappropriate, that is, inconsistent with drug labeling, in as many as 57% of cases [
      • Steinberg B.A.
      • Shrader P.
      • Pieper K.
      • Thomas L.
      • Allen L.A.
      • Ansell J.
      • et al.
      Outcomes registry for better informed treatment of atrial fibrillation (ORBIT-AF) II investigators. Frequency and outcomes of reduced dose non-vitamin K antagonist anticoagulants: results from ORBIT-AF II (the outcomes registry for better informed treatment of atrial fibrillation II).
      ]. Inappropriate dosing, and especially underdosing, has been associated in turn, with unfavourable outcomes [
      • Steinberg B.A.
      • Shrader P.
      • Pieper K.
      • Thomas L.
      • Allen L.A.
      • Ansell J.
      • et al.
      Outcomes registry for better informed treatment of atrial fibrillation (ORBIT-AF) II investigators. Frequency and outcomes of reduced dose non-vitamin K antagonist anticoagulants: results from ORBIT-AF II (the outcomes registry for better informed treatment of atrial fibrillation II).
      ]. When interpreting the above findings, considerations on both pharmacology of DOACs, and design of phase III trials of DOACs against warfarin in NVAF [
      • Connolly S.J.
      • Ezekowitz M.D.
      • Yusuf S.
      • Eikelboom J.
      • Oldgren J.
      • Parekh A.
      • et al.
      RE-LY steering committee and investigators. Dabigatran versus warfarin in patients with atrial fibrillation.
      ,
      • Patel M.R.
      • Mahaffey K.W.
      • Garg J.
      • Pan G.
      • Singer D.E.
      • Hacke W.
      • et al.
      ROCKET AF investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.
      ,
      • Granger C.B.
      • Alexander J.H.
      • McMurray J.J.
      • Lopes R.D.
      • Hylek E.M.
      • Hanna M.
      • et al.
      ARISTOTLE committees and investigators. Apixaban versus warfarin in patients with atrial fibrillation.
      ,
      • Giugliano R.P.
      • Ruff C.T.
      • Braunwald E.
      • Murphy S.A.
      • Wiviott S.D.
      • Halperin J.L.
      • et al.
      ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation.
      ] should be made.

      Keywords

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