Anticoagulants play an important role in reducing complications and mortality associated with thromboembolic disease. For some time, vitamin K antagonists (VKAs) have been the main drugs used for long-term oral anticoagulant therapy, but because of the significant limitations of VKAs over the past decade, pharmacological research has led to the development of new direct acting oral anticoagulants (DOACs). Direct acting oral anticoagulants have a rapid onset of action with peak levels within 2–4 hours and a half-life of about 12 hours, which is much shorter than that of vitamin K antagonists, a more predictable anticoagulant effect, no need for dose selection, routine laboratory monitoring of pharmacodynamic effects, and a lower frequency of clinically significant drug-drug interactions compared with warfarin. But anticoagulants can still cause serious adverse drug reactions (ADRs) in the form of hemorrhagic complications in hospitalized patients, as confirmed in studies. Currently, clinicalpharmacological technologies of personalized medicine such as pharmacogenetic and pharmacokinetic studies are considered as promising approaches to improve the safety of modern pharmacotherapy, allowing the prediction and prevention of various ADRs. In addition, there are emerging studies showing the importance of genetic features of patients in relation to the metabolism of oral anticoagulants, as well as described clinical situations where different gene polymorphisms, could be responsible for changes in the pharmacokinetics of DOACs. This article reviews clinical cases in which pharmacogenetic testing and therapeutic drug monitoring are used to optimize the clinical efficacy and maximum safety of anticoagulant therapy with apixaban and rivaroxaban.
Cardiovascular disease is the most common cause of death in the world. For almost 60 years vitamin K antagonists (VKAs) have been the mainstay of anticoagulant therapy, but in recent years direct oral anticoagulants (DAACs) have become the anticoagulant of choice, as they have many well-known advantages: more predictable anticoagulant effect, no need for dose selection (there is a need for dose adjustment only for renal dysfunction), routine laboratory monitoring of pharmacodynamic effect (except in special clinical situations), less frequency of clinically significant drug interactions compared with warfarin, and less dependence on patient genetic characteristics. The main indications for POAC are: prevention of venous thromboembolism in patients who have undergone endoprosthesis of lower limbs, prevention of stroke and systemic embolism in patients with atrial fibrillation, treatment and prevention of recurrent deep vein thrombosis (DVT) and pulmonary embolism. The administration of direct oral anticoagulants (DOACs) has long been considered a major therapeutic advance, mainly because they do not require therapeutic monitoring. Despite this, POACs, like vitamin K antagonists, can still cause major and clinically significant minor bleeding, even when used correctly. Considering that POAC patients are often older and have multiple comorbidities, polypragmasy is widespread. Drug interactions involving POACs are important contributors to the increased risk of bleeding. Awareness of these drug interactions and how to address them is critical to optimizing treatment while reducing the risk of bleeding. This review provides an overview of POAC metabolism, the most common drugs that may interact with POACs, and ways to eliminate these interactions.
Aim. To investigate the effect of ABCB1 gene carriage and interdrug interactions on apixaban pharmacokinetics and clinical outcomes in patients with atrial fibrillation and deep vein thrombosis.Material and methods. Patients hospitalized at Yudin State Clinical Hospital participated in the study. A total of 92 patients (50 patients received apixaban and 42 – rivaroxaban) with non-valvular atrial fibrillation and deep vein thrombosis were included. Genotyping was performed by real-time polymerase chain reaction. Direct oral anticoagulants concentrations were measured using an electrospray ionization mass spectrometer in positive ionization mode.Results. In our study we found that in patients carrying the CT+TT ABCB1 (rs4148738) C>T genotype encoding the carrier protein (P-gp), the plasma concentration of rivaroxaban was statistically significantly higher p= 0.026. In addition, we found that patients taking apixaban together with a CYP3A4/P-gp inhibitor were 3.5 times more likely to have hemorrhagic complications than those without inhibitors p = 0.004.Conclusion. Our study revealed that the plasma concentration of rivaroxaban was higher in patients carrying the ABCB1 (rs4148738) C>T polymorphism T allele. And patients taking apixaban together with CYP3A4/P-gp inhibitor had higher risk of hemorrhagic complications in comparison with patients not taking such drugs. Further studies are needed on the influence of pharmacogenetics and pharmacokinetics on the safety and efficacy profile of apixaban and rivaroxaban, taking into account the trend of systemic approach to optimization of anticoagulant therapy of direct oral anticoagulants based on pharmacokinetic, pharmacogenetic biomarkers.
Aims: To study the readiness of Russian physicians with experience and younger physicians undergoing clinical residency and postgraduate education to apply pharmacogenetic testing in their clinical practice. Materials & methods: The sociological study involved physicians (n = 378) living in different regions of the Russian Federation, as well as residents and graduate students (n = 185) of the Russian Medical Academy of Continuing Professional Medical Education. The survey consisted of 35 questions, and 23 were created on the online platform of professional surveys, Testograf.ru. Results: Every second respondent was willing to use pharmacogenetic testing in clinical practice to predict the efficacy and safety of medications in patients with cardiovascular disease (p = 0.06). Factors impeding the clinical implementation of pharmacogenetic testing in Russia were identified: physicians' ignorance of pharmacogenetics (p = 0.015), a lack of pharmacogenetic testing in clinical guidelines and treatment standards (p = 0.175) and a lack of economic justification for using pharmacogenetic testing (p = 0.320). Conclusion: Russian physicians have a positive attitude toward pharmacogenetic testing. However, the level of test implementation remains low.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.