Dataset Information

Polymorphisms of CYP2C92, CYP2C93 and VKORC1 genes related to time in therapeutic range in patients with atrial fibrillation using warfarin.

ABSTRACT:

Introduction

Warfarin continues to be the most widely used anticoagulant in clinical practice around the world for the prevention of thromboembolic events in patients with atrial fibrillation (AF). The evaluation of the quality of anticoagulation control, estimated by time in therapeutic range (TTR), is accepted as a good method to evaluate the quality of anticoagulation. The variability of TTR can be explained by the presence of variants of the CYP2C9 and VKORC1 genes.

Methods

This study examined the association between polymorphisms of the CYP2C9 and VKORC1 genes and control of oral anticoagulation, through TTR, in patients with AF. A cross-sectional study was conducted within a cohort follow-up. The study comprised of 317 patients with AF, using warfarin, who were followed up for one year. The genotyping of genes CYP2C9 (rs1057910), (rs1799853) and VKORC1 (rs923231) was performed by PCR in real time, using TaqMan probes.

Results

Patients who had variant genotypes for the CYP2C9*3 gene (rs1057910) presented higher TTR (TTR 81-100%) when compared to when compared to the <45% and 46-60% TTR groups (p=0.005 and p=0.002, respectively). Regarding VKORC1 (rs923231), patients who had the variant genotype for the VKORC1 (rs923231) gene also presented a higher TTR (TTR 81-100%), when when compared to the <45% and 46-60% TTR groups (p=0.005 and p=0.004, respectively). In a multivariate model, VKORC1 (rs923231) remained associated for comparisons with the TTR groups (<45% vs 81-100% groups, p=0.01; and 46-60% vs 81-100% groups, p=0.01).

Conclusion

The genotypes of the CYP2C9*3 (AA) and VKORC1 -1639 (GG) genes were associated with the worst quality of anticoagulation control (TTR) in patients with AF using warfarin in the northeast of Brazil.

SUBMITTER: da Silveira MMBM

PROVIDER: S-EPMC6684853 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Polymorphisms of <i>CYP2C92, CYP2C93</i> and <i>VKORC1</i> genes related to time in therapeutic range in patients with atrial fibrillation using warfarin.

da Silveira Maria Mariana Barros Melo MMBM Melo Leiliandry de Araújo LA Gomes Filipe Maia Ferreira FMF Andrade Leonardo José de Cupertino Barreto da Rocha LJCBDR Serur Isabela Paulino IP Piscoya Isabelle Cecília de Vasconcellos ICV Gueiros Raposo Marina RM Palmeira do Ó Kleyton K de Lima Raul Emídio RE Brasileiro Victor Arthur Eulálio VAE Vasconcelos Luydson Richardson Silva LRS Sobral Filho Dário Celestino DC

The application of clinical genetics 20190802

<h4>Introduction</h4>Warfarin continues to be the most widely used anticoagulant in clinical practice around the world for the prevention of thromboembolic events in patients with atrial fibrillation (AF). The evaluation of the quality of anticoagulation control, estimated by time in therapeutic range (TTR), is accepted as a good method to evaluate the quality of anticoagulation. The variability of TTR can be explained by the presence of variants of the <i>CYP2C9</i> and <i>VKORC1</i> genes.<h4> ...[more]

PMID: 31447576

Similar Datasets

Project description:The polymorphisms of cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex 1 (VKORC1) are important genetic factors for warfarin dose determinations. The present study aimed to investigate the contribution of the CYP2C9 and VKORC1 genotypes to warfarin dose requirement in atrial fibrillation (AF) patients, and to evaluate the clinical application of a warfarin-dosing algorithm. A total of 122 AF patients with a target international normalized ratio of 2.0 to 3.0 were included to determine the genotypes of CYP2C9 (rs1057910) and VKORC1 (rs9923231). A warfarin-dosing algorithm was developed based on age, height, and the CYP2C9 and VKORC1 genotypes of AF patients. The results indicated that the mean warfarin daily dose requirement was lower in the CYP2C9*1/*3 genotype compared with those in the homozygous wild-type CYP2C9*1/*1 patients (P<0.05), and was higher in patients with the VKORC1 AG and GG genotypes compared with those with the AA genotype (P<0.05). The multivariate regression model showed that age, height, and the CYP2C9 and VKORC1 genotypes were the best variables for estimating warfarin dose (R2=56.4%). A new warfarin-dosing algorithm was developed and its validity was confirmed in a second cohort of AF patients. During the 50-day follow-up, 63.3% (19/30) of control group patients and 86.7% (26/30) of patients in the experimental group acquired the warfarin maintenance dose. Among all the patients who acquired the warfarin maintenance dose, the mean time elapse from initiation until warfarin maintenance dose was significantly less in the experimental group (25.8±1.7 day) compared to the control group (33.1±1.9 day) (P<0.05). There was significant linear correlation between predicted warfarin maintenance dose and actual dose (r=0.822, P<0.01). In conclusion, a new warfarin-dosing algorithm was developed based on the CYP2C9 and VKORC1 genotypes, and it can shorten the time elapse from initiation until warfarin maintenance dose in AF patients with warfarin therapy.

Project description:Direct oral anticoagulants (DOACs) used in nonvalvular atrial fibrillation (NVAF) are dose-reduced in elderly and patients with impaired renal function. Only reduced dose dabigatran is concluded as having similar stroke risk reduction and lower risk of major bleeding than warfarin in the pivotal studies. In clinical practice, reduced dose is prescribed more often than expected making this an important issue. The objective of this study was to compare effectiveness and safety between reduced dose DOACs and high TTR warfarin treatment (TTR ≥ 70%) in NVAF. A Swedish anticoagulation registry was used in identifying eligible patients from July 2011 to December 2017. The study cohort consisted of 40,564 patients with newly initiated DOAC (apixaban, dabigatran, or rivaroxaban) (11,083 patients) or warfarin treatment (29,481 patients) after exclusion of 374,135 patients due to not being warfarin or DOAC naïve, not being prescribed reduced dose, having previous mechanical heart valve (MHV), or being under 18 years old. The median durations of follow up were 365, 419, 432 and 473 days for apixaban, dabigatran, rivaroxaban and warfarin, respectively. Warfarin TTR identified from Auricula was 70.0%. Endpoints (stroke and major bleeding) and baseline characteristics were collected from hospital administrative registers using ICD-10 codes. Cohorts were compared using weighted adjusted Cox regression after full optimal matching based on propensity scores. DOACs are associated with lower risk of major bleeding (HR with 95% CI) 0.85 (0.78-0.93), intracranial bleeding HR 0.64 (0.51-0.80), hemorrhagic stroke HR 0.68 (0.50-0.92), gastrointestinal bleeding HR 0.81 (0.69-0.96) and all-cause stroke HR 0.87 (0.76-0.99), than warfarin. Apixaban and dabigatran are associated with lower risk of major bleeding, HR 0.70 (0.63-0.78) and HR 0.80 (0.69-0.94), and rivaroxaban is associated with lower risk of ischemic stroke, HR 0.73 (0.59-0.96), with higher major bleeding risk, HR 1.31 (1.15-1.48), compared to warfarin. Apixaban is associated with higher all-cause mortality compared to warfarin, HR 1.12 (1.03-1.21). DOACs are associated with lower risk of major bleeding and all-cause stroke, than high quality warfarin treatment, with exception of rivaroxaban that carried higher risk of major bleeding and lower risk of stroke or systemic embolism. In this large observational registry-based NVAF cohort, DOACs are preferred treatment in patients with indication for DOAC dose reduction, even in a high TTR setting.

Dataset Information

Polymorphisms of CYP2C92, CYP2C93 and VKORC1 genes related to time in therapeutic range in patients with atrial fibrillation using warfarin.

Introduction

Methods

Results

Conclusion

Publications

Polymorphisms of <i>CYP2C92, CYP2C93</i> and <i>VKORC1</i> genes related to time in therapeutic range in patients with atrial fibrillation using warfarin.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Polymorphisms of CYP2C9*2, CYP2C9*3 and VKORC1 genes related to time in therapeutic range in patients with atrial fibrillation using warfarin.

Introduction

Methods

Results

Conclusion

Publications

Polymorphisms of <i>CYP2C9*2, CYP2C9*3</i> and <i>VKORC1</i> genes related to time in therapeutic range in patients with atrial fibrillation using warfarin.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Polymorphisms of CYP2C92, CYP2C93 and VKORC1 genes related to time in therapeutic range in patients with atrial fibrillation using warfarin.

Polymorphisms of <i>CYP2C92, CYP2C93</i> and <i>VKORC1</i> genes related to time in therapeutic range in patients with atrial fibrillation using warfarin.