Systematic errors in the choice of dose level of direct oral anticoagulants: urgency of an issue and approaches to its solution

Abstract

The article presents updated information on the frequency of use of non-recommended low dosing of direct oral anticoagulants (dabigatran, rivaroxaban, apixaban and edoxaban). It gives substantiation of the urgency of the issue of providing the maximum efficiency of the use of anticoagulants in clinical practice, taking into account the high prevalence of atrial fibrillation and the pharmacological characteristics of the most commonly used drugs. The effects of such an unreasonable reduction in anticoagulant doses in elderly and senile patients are discussed. The results of recent observational studies that assessed the relationship between the use of direct oral anticoagulants and the risk of adverse clinical outcomes are presented. The data on the relationship between the use of unreasonably low dosing of anticoagulants in patients with atrial fibrillation, which were recently obtained during the implementation of the GARFIELD-AF registry, are discussed. The data on a rather high variability of concentrations of direct oral anticoagulants are presented. The frequency of using apixaban in an unreasonably reduced dose, as well as the effects of using non-recommended doses of apixaban hold a specific place in the article. The unreasonableness of attempts to further reduce the risk of bleeding due to unreasonable reduction of apixaban dosing is emphasized, taking into account the stable data on the high safety of recommended dosing of apixaban, as well as the possible decrease in the effect if the dose reduction is not recommended. The data on the criteria for dose reduction, which are adopted in different countries, are presented. The proposed terms to designate different doses of direct oral anticoagulants, depending on their study in the course of large, randomized trials are discussed.