Pharmacogenetic Aspects of New Oral Anticoagulants Application

Kryukov, A. V.; Сычев, Д. А.; Tereshchenko, O. V.

doi:10.20996/1819-6446-2017-13-3-416-421

Cited by 5 publications

(4 citation statements)

References 6 publications

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“…Apixaban reversibly inhibits factor Xa of the coagulation cascade and was approved by the FDA in 2012 as a preventive treatment for stroke in patients with NVAF and the treatment of pulmonary embolism and deep vein thrombosis. 9 – 11 It is preferably used in patients with risk factors (previous history of stroke, hypertension, diabetes mellitus, heart failure, or age ⩾75 years). 7 The evidence base for apixaban to prevent thromboembolic events in such patients is presented in two studies – AVERROES and ARISTOTLE.…”

Section: Resultsmentioning

confidence: 99%

“…The drug has a bioavailability of approximately 50%, a half-life ranging between 8 and 15 h, and reaches its peak plasma concentration within 3 or 4 h after ingestion. 7 , 9 – 11 , 24 Food has no clinically significant effect on the bioavailability of apixaban. 28 Frost et al.…”

Section: Resultsmentioning

confidence: 99%

“…These patients exhibited diverse polymorphisms of the ABCB1 gene, including five with the CC genotype, nine with the CT genotype, three with the TT genotype for rs1045642 , four with the CC genotype, seven with the CT genotype, and six with the TT genotype for rs4148738 . 10 …”

Section: Resultsmentioning

confidence: 99%

“… 4 , 9 DOACs include dabigatran (an inhibitor of clotting factor IIa), apixaban, rivaroxaban, and edoxaban (inhibitors of clotting factor Xa). 7 , 9 , 10 DOACs share common characteristics: they have a shorter half-life (lasting between 5 and 17 h) compared to warfarin, pose a reduced risk of drug interactions, do not require laboratory monitoring, offer fixed dosages, and have a broad ‘therapeutic window’. 1 , 7 , 11 When the efficacy of DOACs was compared with that of another representative of long-acting vitamin K antagonists, phenprocoumon, the risks of thromboembolic complications were significantly higher; however, the risk of bleeding was lower than that of phenprocoumon.…”

Section: Introductionmentioning

confidence: 99%

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Gene polymorphism as a cause of hemorrhagic complications in patients with non-valvular atrial fibrillation treated with oral vitamin K-independent anticoagulants

Abdrakhmanov,

Shaimerdinova,

Suleimen

et al. 2024

Therapeutic Advances in Cardiovascular Disease

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Atrial fibrillation (AF) accounts for 40% of all cardiac arrhythmias and is associated with a high risk of stroke and systemic thromboembolic complications. Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that have been proven to prevent stroke in patients with non-valvular AF. This review summarizes the pharmacokinetics, pharmacodynamics, and drug interactions of DOACs, as well as new data from pharmacogenetic studies of these drugs. This review is aimed at analyzing the scientific literature on the gene polymorphisms involved in the metabolism of DOACs. We searched PubMed, Cochrane, Google Scholar, and CyberLeninka (Russian version) databases with keywords: ‘dabigatran’, ‘apixaban’, ‘rivaroxaban’, ‘edoxaban’, ‘gene polymorphism’, ‘pharmacogenetics’, ‘ ABCB1’, ‘ CES1’, ‘ SULT1A’, ‘ ABCG2’, and ‘ CYP3A4’. The articles referred for this review include (1) full-text articles; (2) study design with meta-analysis, an observational study in patients taking DOAC; and (3) data on the single-nucleotide polymorphisms and kinetic parameters of DOACs (plasma concentration), or a particular clinical outcome, published in English and Russian languages during the last 10 years. The ages of the patients ranged from 18 to 75 years. Out of 114 reviewed works, 24 were found eligible. As per the available pharmacogenomic data, polymorphisms affecting DOACs are different. This may aid in developing individual approaches to optimize DOAC pharmacotherapy to reduce the risk of hemorrhagic complications. However, large-scale population studies are required to determine the dosage of the new oral anticoagulants based on genotyping. Information on the genetic effects is limited owing to the lack of large-scale studies. Uncovering the mechanisms of the genetic basis of sensitivity to DOACs helps in developing personalized therapy based on patient-specific genetic variants and improves the efficacy and safety of DOACs in the general population.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Gene polymorphism as a cause of hemorrhagic complications in patients with non-valvular atrial fibrillation treated with oral vitamin K-independent anticoagulants

Abdrakhmanov,

Shaimerdinova,

Suleimen

et al. 2024

Therapeutic Advances in Cardiovascular Disease

View full text Add to dashboard Cite

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Pharmacogenetics of new oral anticoagulants

2023

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The review presents modern studies the effect of genetic polymorphisms on the efficienty and safety of therapy with new oral anticoagulants. Hepatic carboxylesterase encoded by the CES1 gene and P-glycoprotein encoded by the ABCB1 gene affect dabigatran pharmacokinetics. The role of glucuronidation enzymes (UGT2B15, UGT1A9, UGT2B7) involved in active dabigatran metabolism is poorly understood. An increase in the peak apixaban concentration was noted in patients with the rs4148738 polymorphism of the ABCB1 gene. Polymorphisms rs776746 and rs77674 of the CYP3A5 gene affect concentration of apixaban in Asian patients and thus increased the bleeding risk. The effect SULT1A1 sulfotransferase on the metabolism of apixaban has yet to be studied. The BCRP protein encoded by the ABCG2 gene is a poorly studied but promising direction for the pharmacokinetics of apixaban. ABCB1 and CYP3A4 of the cytochrome P450 system affect the rivaroxaban metabolism, however, the number of studies devoted to examining the effect of polymorphisms of these genes on the rivaroxaban pharmacokinetics limited. Thus, large studies are needed to clarify the clinical relevance of genotyping in target patients taking new oral anticoagulants.

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