&lt;p&gt;&lt;em&gt;CYP2C19*17&lt;/em&gt; May Increase the Risk of Death Among Patients with an Acute Coronary Syndrome and Non-Valvular Atrial Fibrillation Who Receive Clopidogrel and Rivaroxaban&lt;/p&gt;

Sychev, D.A.; Батурина, О. А.; Мирзаев, К. Б.; Rytkin, Eric; Ivashchenko, Dmitriy V.; Андреев, Д. А.; Рыжикова, К. А.; Grishina, Elena A.; Бочков, П. О.; Шевченко, Р. В.

doi:10.2147/pgpm.s234910

Cited by 12 publications

(12 citation statements)

References 52 publications

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“…The gene polymorphism of ABCB1 may cause P-gp expression to (Sychev et al, 2020;Wang et al, 2021). The genetic factor CYP2C19 was proved to be associated with the risk of bleeding complications in situations of rivaroxaban antithrombotic therapy (Zhang et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Effect of ABCB1 gene variants on rivaroxaban pharmacokinetic and hemorrhage events occurring in patients with non‐valvular atrial fibrillation

Zhang

Qin

et al. 2022

Biopharm & Drug Disp

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Hemorrhage events occur most frequently in anticoagulant therapy for non-valvular atrial fibrillation (NVAF). Rivaroxaban is used widely for routine anticoagulation care. Genetic polymorphisms are thought to contribute to the wide intraindividual variability seen in rivaroxaban metabolism and the anticoagulant response. The aim of this study was to evaluate the effect of drug transport related single-nucleotide polymorphisms (SNPs) on rivaroxaban metabolism and on the risk of a hemorrhage event. A total of 216 Chinese patients with NVAF were enrolled in the study.Rivaroxaban was used for anticoagulation therapy. Rivaroxaban plasma concentrations were detected using a validated ultra-performance liquid chromatographytandem mass spectrometry (UPLC-MS/MS) method. Seven SNPs in four genes were genotyped using the Sanger dideoxy DNA sequencing method. Associations between genotype variants, the incidence of hemorrhage events, and the time of bleeding were analyzed. ABCB1 2677G (rs2032582) variation was highly associated with the dose-adjusted rivaroxaban peak concentration in plasma (C max /D) (p = 0.025, FDR = 0.042). The ABCB1 G allele carriers had a higher rivaroxaban C max /D than non-carriers. Logistic regression showed that rivaroxaban C max /D and ABCB1 genotype variants were associated with a higher incidence of hemorrhage events. No statistically significant difference was found between ABCB1 genotypes and the time of bleeding after anticoagulant therapy in 30 days. These results indicated that ABCB1 2677G (rs2032582) genetic variant affects the rivaroxaban C max /Dose and the incidence of hemorrhage events significantly.

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Section: Discussionmentioning

confidence: 99%

Effect of ABCB1 gene variants on rivaroxaban pharmacokinetic and hemorrhage events occurring in patients with non‐valvular atrial fibrillation

Zhang

Qin

et al. 2022

Biopharm & Drug Disp

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“…A recent trial found that a clopidogrel prescription after STEMI, using genotype-guided point of care, produced less bleeding and equal ischaemic events when compared with ticagrelor or prasugrel [99]. Moreover, similar results were documented in AF patients with interventional treatment [100,101]. Thus, genetic testing could be the answer when the thrombotic risk is not high and using clopidogrel in a DAT regimen represents the best option to reduce bleeding complications.…”

Section: Potent P2y12 Inhibitors Versus Clopidogrelmentioning

confidence: 93%

Management of antithrombotic therapy in patients with atrial fibrillation and acute coronary syndromes

Pop¹,

Țînț²,

Petriş³

2021

Rev. Cardiovasc. Med.

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If atrial fibrillation (AF) and acute coronary syndrome (ACS) coexist, they should be treated with combined antithrombotic therapy. To reduce the risk of bleeding while maintaining the desired antithrombotic effect, choices should be made for each patient according to the balance between the bleeding and the thrombotic risk. There are many ways to select the type and dose of the oral anticoagulant (OAC) and P2Y12 inhibitors. As a rule of thumb, aspirin and P2Y12 inhibitors should be recommended to all patients. The duration of this combination therapy is a matter of debate; available data promote an initial period of one to four weeks of triple antithrombotic association with aspirin and P2Y12 inhibitors (clopidogrel in the absence of high ischaemic risk) and preferable direct oral anticoagulants (DOACs). On discontinuing aspirin, double therapy with P2Y12 inhibitors and a DOAC provides similar efficacy and superior safety for many patients on ACS medical or interventional treatment, especially if the risk of bleeding is high and that of thrombosis is low. Further studies are needed to clarify the concerns for a slight augmentation in the number of ischaemic cases (myocardial infarction and stent thrombosis) with double antithrombotic regimen in patients at high ischaemic risk.

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“…The POPular Genetics trial found that genotype-guided clopidogrel prescription after ST-elevation myocardial infarction (STEMI) without an indication for OAC showed equal MACE, but less bleeding, compared to standard treatment with ticagrelor or prasugrel [ 38 ]. A suggestion of benefit has also been described in patients with AF undergoing PCI [ 39 , 40 ]. Therefore, if available, before prescribing more potent P2Y 12 inhibition, genetic testing might be reasonable to consider if equal antithrombotic efficacy can be expected with clopidogrel to reduce bleeding complications and in the absence of high ischaemic risk.…”

Section: Choice Of Antiplatelet Agentmentioning

confidence: 99%

Antithrombotic Therapy in Patients with Atrial Fibrillation and Acute Coronary Syndrome

Bor

Gorog

2020

JCM

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Acute coronary syndrome and atrial fibrillation are both common and can occur in the same patient. Combination therapy with dual antiplatelet therapy and oral anticoagulation increases risk of bleeding. Where the two conditions coexist, careful consideration is needed to determine the optimal antithrombotic treatment to reduce the risks of future ischaemic events associated with both conditions. Choices can be made in intraprocedural anticoagulation, type and dosing of oral anticoagulant, duration of combination therapy, and selection of P2Y12 inhibitor including genetic testing. This review article provides an overview of the available evidence to support clinicians in finding the delicate balance between antithrombotic efficacy and bleeding risk in patients with acute coronary syndrome and atrial fibrillation.

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<p><em>CYP2C19*17</em> May Increase the Risk of Death Among Patients with an Acute Coronary Syndrome and Non-Valvular Atrial Fibrillation Who Receive Clopidogrel and Rivaroxaban</p>

Cited by 12 publications

References 52 publications

Effect of ABCB1 gene variants on rivaroxaban pharmacokinetic and hemorrhage events occurring in patients with non‐valvular atrial fibrillation

Effect of ABCB1 gene variants on rivaroxaban pharmacokinetic and hemorrhage events occurring in patients with non‐valvular atrial fibrillation

Management of antithrombotic therapy in patients with atrial fibrillation and acute coronary syndromes

Antithrombotic Therapy in Patients with Atrial Fibrillation and Acute Coronary Syndrome

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