Reviewing recent literature of advances in arrhythmia therapy, I have found most interesting the emergence of antidotes, both general and specific, for the non-vitamin K antagonist oral anticoagulants (NOACs). NOACs offer a relative 50 % reduction in the risk of intracranial haemorrhage and haemorrhagic stroke compared with warfarin that is also maintained in the elderly. There are no clear interactions with food, and no need for frequent laboratory monitoring and dose adjustments.1–3 Their main problems so far have been the lack of antidotes and specific assays to measure anticoagulant effect, and considerably higher cost than warfarin.4 It is, therefore, of major clinical importance to see specific antidotes emerging in phase 1 and 2 trials.
Non-specific procoagulant agents such as 3- or 4-factor prothrombin complex concentrates (PCCs) and activated factor VIIa can be used as antidotes for dabigatran.5–7 Specific antidotes are also under study. Idarucizumab, a fully humanised antibody fragment, or Fab, is investigated as a specific antidote of dabigatran, and also reversed its effects and, unlike PCCs, was not associated with over-correction of thrombin generation.7 Four-factor PCCs are also general antidotes for Xa inhibitors such as apixaban, rivaroxaban
and endoxaban.6 Specific antidotes such as aripazine (PER977, 100–200 mg), a synthetic molecule that
binds specifically to unfractionated heparin and low-molecular-weight heparin, and the recombinant factor
Xa andexanet have been successfully used for edoxaban and rivaroxaban. Aripazine also binds in a similar way to dabigatran, but further clinical experience is needed in this setting.
Clinical experience with the NOACs compared with warfarin is too limited to unequivocally pronounce dead this useful old drug. Nevertheless, a new era has begun, and the results of clinical trials and ‘real-life’ registries are eagerly awaited in this respect.
Dr Demosthenes Katritsis, Editor-in-Chief
Athens Euroclinic, Greece and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, US