Abstract
Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that are increasingly used worldwide. Taking into account their widespread use for the prevention of thromboembolism in cardiology, neurology, orthopedics, and coronavirus disease 2019 (COVID 19) as well as their different pharmacokinetics and pharmacogenetics dependence, it is critical to explore new opportunities for DOACs administration and predict their dosage when used as monotherapy or in combination with other drugs. In this review, we describe the details of the relative pharmacogenetics on the pharmacokinetics of DOACs as well as new data concerning the clinical characteristics that predetermine the needed dosage and the risk of adverse drug reactions (ADRs). The usefulness of genetic information before and shortly after the initiation of DOACs is also discussed. The reasons for particular attention to these issues are not only new genetic knowledge and genotyping possibilities, but also the risk of serious ADRs (primarily, gastrointestinal bleeding). Taking into account the effect of the carriership of single nucleotide variants (SNVs) of genes encoding biotransformation enzymes and DOACs metabolism, the use of these measures is important to predict changes in pharmacokinetics and the risk of ADRs in patients with a high risk of thromboembolism who receive anticoagulant therapy.
Highlights
Thromboembolism is a serious complication of non-valvular atrial fibrillation (AF) [1]
About ten different single nucleotide variants (SNVs) for the CYP2J2 gene are known, but their clinical role was mainly studied in the context of coronary heart disease (CAD) and arterial hypertension, since isoenzyme CYP2J2 encoded by this gene plays a role in the metabolism of arachidonic acid [60]
The PGx variants can affect the pharmacokinetics of the direct oral anticoagulants (DOACs), especially co-administration DOACs with other drugs (Tables 1 and 2), which are prescribed to patients with cerebrovascular diseases and comorbid disorders
Summary
Thromboembolism (such as stroke and systemic embolism) is a serious complication of non-valvular atrial fibrillation (AF) [1]. In the absence of preventive measures, before widespread use of anticoagulant therapy in clinical practice, the percentage of venous thromboembolic complications in lower limb arthroplasty (deep vein thrombosis and PE) reached 15–30% of the total number of cases. Long-term use of anticoagulants is necessary to prevent thromboembolic complications in patients with high risk of thromboembolism. K antagonists (a coumarin derivative warfarin, acenocumarol, and phenindione) and indirect thrombin inhibitors (heparins) have been used as drugs to prevent the occurrence of thromboembolic complications [5,6]. Despite its effectiveness, coumarin or heparins therapy has some limitations. The therapeutic effect of anticoagulant therapy will not be achieved. Balancing the effectiveness and safety of anticoagulant therapy is a difficult task in real clinical practice. It is necessary to take into account the pharmacogenetic characteristics of the individual that can affect the effectiveness and safety of the DOACs use
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