Anticoagulant therapy with apixaban based on a pharmacogenetic approach: a course to safety

Abstract

For the past 60 years, vitamin K antagonists (VKAs) have been the main drugs used for long-term oral anticoagulant therapy. Because of the significant limitations of AVCs, direct-acting oral anticoagulants (DOAKs) have been developed over the past decade. DOAKs have a predictable pharmacokinetic profile and lack the disadvantages of vitamin K antagonists. Apixaban is an oral direct-acting factor Xa inhibitor used for the prevention of thromboembolic complications in patients with non-valvular atrial fibrillation (AF) and deep vein thrombosis. Despite the use of recommended dosages, some patients may still experience bleeding or lack the desired anticoagulant effect. With this in mind, it is critical to explore new uses for direct oral anticoagulants and to predict their dosage when used in monotherapy or in combination with other drugs. In addition, recent studies have documented individual variability in plasma POAC levels. DOAC pharmacogenetics is a relatively new area of research. There is a need to understand the role of pharmacogenetics in adapting anticoagulant therapy according to a patient’s genetic characteristics. In this scientific review of current data, we detail the pharmacokinetics and pharmacogenetics of apixaban as well as new data concerning the clinical characteristics that predetermine the necessary dosage and risk of adverse drug reactions (ADRs). Indeed, the results obtained to date from basic and clinical studies certainly indicate an undeniable influence of genomic changes on the pharmacokinetics of POACs.