[Low or reduced? Semantics of the doses of new oral anticoagulants]

The four new oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban and edoxaban are marketed in two doses each for the prevention of stroke and/or systemic thromboembolism in non-valvular atrial fibrillation (NVAF). The meaning and indications for use of the lower dose compared with the higher dose are, however, different between the thrombin-inhibitor dabigatran on the one hand and the activated factor X (Xa) inhibitors on the other. These differences stem from the different design of the registration studies where NOACs were compared with warfarin for the prevention of stroke and/or systemic thromboembolism in patients with NVAF. While in the RE-LY study, two different intensities of dabigatran treatment (150 and 110 mg bid) were evaluated in the same population, in the ROCKET AF, ARISTOTLE and ENGAGE AF-TIMI 48 studies two different populations were exposed to the same intensity of treatment, which was obtained however with the selective use of two doses of rivaroxaban (20/15 mg/die), apixaban (5/2.5 mg bid) and edoxaban (60/30 mg/die). With the two doses of dabigatran, efficacy and safety were proportional to treatment intensity. With the two doses of factor Xa inhibitors, the same effect on efficacy and safety was achieved (with the exception of edoxaban, which was further safer with dose reduction). The choice of the dose of dabigatran is therefore discretionary (except for patients aged ≥80 years and/or treated with verapamil in whom only 110 mg bid can be prescribed), whereas that of factor Xa inhibitors is obligated. If dabigatran doses are properly defined as high and low and those of factor Xa inhibitors full and reduced, it is useful to memorize that in this context "low" should be semantically considered an adjective while "reduced" a participle.