scholarly journals GENETIC POLYMORPHISMS OF CYTOCHROME P450 2C9, VITAMIN K EPOXIDE-REDUCTASE SUBUNIT 1 AND WARFARIN DOSING IN PATIENTS WITH PERMANENT ATRIAL FIBRILLATION

2016 ◽  
Vol 1 (4) ◽  
pp. 18-22
Author(s):  
A O Rubanenko ◽  
Yu V Shchukin
Keyword(s):  
Atrial Fibrillation ◽  
Genetic Polymorphisms ◽  
Warfarin Therapy ◽  
Warfarin Dose ◽  
Cytochrome P450 2C9 ◽  
Risk Of Bleeding ◽  
Permanent Atrial Fibrillation ◽  
Epoxide Reductase ◽  
Warfarin Dosing ◽  
Permanent Form

Aim - to assess the influence of genetic polymorphisms of CYP2C9 and VKORC1 on warfarin dosing in patients with permanent form of atrial fibrillation. Methods. The study included examination of 100 patients with coronary heart disease and permanent form of atrial fibrillation; mean age 60.5±5.8 years. Conclusion. In patients with permanent form of atrial fibrillation, genotypes CYP2C9*1/*3, TT and GG genotypes of VKORC1 are associated with low warfarin dose, compared to other genotypes. Genotype CYP2C9*1/*3 increases the risk of bleeding complication during warfarin therapy.

Evaluation of an Initiation Regimen of Warfarin for International Normalized Ratio Target 2.0 to 3.0

2021 ◽  
pp. 875512252110341
Author(s):  
Sahimi Mohamed ◽  
Chan Mei Fong ◽  
Yew Jie Ming ◽  
Ahlam Naila Kori ◽  
Sopian Abdul Wahab ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Warfarin Therapy ◽  
Warfarin Dose ◽  
Asian Population ◽  
International Normalized Ratio ◽  
Efficacy And Safety ◽  
Risk Of Bleeding ◽  
Number Of Patients ◽  
Inpatient Settings ◽  
The Mean

Background: he number of patients on warfarin therapy is rising steadily. Although warfarin is beneficial, it carries a high risk of bleeding, especially if the international normalized ratio (INR) values exceed 3.0. Currently, no warfarin initiation regimens have been developed for the Asian population, especially for Malaysians. Objective: This article describes the efficacy and safety of a new initiation regimen for warfarin among warfarin-naive patients. Method: Data were retrospectively collected from the ambulatory and inpatient settings. Results: A total of 165 patients who each had a target INR of 2.0 to 3.0 were included in the study. The mean age was 57.2 years and 94 patients were male. A total of 108 patients used Regimen 1 (5 mg/5 mg/3mg) and the rest of the patients used Regimen 2 (5 mg/3 mg/3 mg). Most patients used warfarin either for atrial fibrillation (52.1%) or for venous thromboembolism (29.7%). Overall, 88 of the patients had INR values above 50% from the baseline on Day 4. Additionally, 13 patients had INR values of >3.2, which required withholding and lower dose of warfarin. The predicted weekly maintenance warfarin dose (23 ± 0.5 mg/week) was found to have correlated closely with the actual maintenance dose (22.8 ± 0.5 mg/week; r2 = 0.75). Nearly two thirds (70.3%) of the patients achieved the target INR on Day 11. Conclusion: The warfarin initiation regimens in this study was simple, safe, and suitable to be used in both ambulatory and inpatient settings for managing warfarin therapy.

Abstract 15396: Atrial Fibrillation Bleeding Risk and Prediction While Treated With Direct Oral Anticoagulants in Warfarin Naïve and Experienced Patients

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Alexander C Perino ◽  
Krishna Pundi ◽  
Jun Fan ◽  
Susan K Schmitt ◽  
Mitra Kothari ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Warfarin Therapy ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Risk ◽  
Risk Of Bleeding ◽  
Warfarin Treatment ◽  
Treatment Analysis ◽  
Using Data ◽  
Favorable Safety

Introduction: Direct oral anticoagulants (DOAC) are guideline-recommended over warfarin for stroke prevention in atrial fibrillation (AF). However, patients who are DOAC eligible are commonly maintained on warfarin. We sought to evaluate bleeding risk and prediction while on DOAC treatment (both for warfarin-naïve and -experienced patients) as compared to warfarin. Methods: We performed a retrospective cohort study using data from the Veteran Affairs health care system. We included patients with a prescription for warfarin and/or DOAC from 10/1/2010 to 9/30/2017 with an AF encounter in the 90 days prior to 30 days after prescription. We categorized DOAC treated patients as warfarin-naïve or -experienced and performed an on-treatment analysis to determine bleeding incidence and HAS-BLED score discrimination. In adjusted analyses, we compared risk of bleeding while treated with DOAC (both for warfarin-naïve and -experienced patients) to warfarin. Results: The analysis cohort included 99,143 patients treated with warfarin (71±10 years, HAS-BLED 2.6±1.2) and 73,732 and 26,760 patients treated with DOAC who were warfarin-naïve (74±10 years, HAS-BLED 2.4±1.0) and -experienced (71±9 years, HAS-BLED 2.8±1.1), respectively. DOAC patients with warfarin experience had more prior bleeds (DOAC, warfarin-experienced: 11.9%; DOAC, warfarin-naïve: 4.5%; warfarin: 6.2%; p<0.001 for both). Risk of intracranial bleeding was substantially lower while on DOAC treatment (both for warfarin-naïve and -experienced patients) as compared to warfarin ( Table ). HAS-BLED discrimination for bleeding outcomes, intracranial or any bleeding, was modest ( Table ). Conclusion: DOAC treatment had a favorable safety profile compared to warfarin treatment, even for DOAC treated patients with warfarin-experience who had more prior bleeds. These data argue against maintaining DOAC eligible patients on warfarin therapy regardless of HAS-BLED score.

Effects of rare CYP2C9 alleles on stable warfarin doses in Chinese Han patients with atrial fibrillation

2020 ◽  
Vol 21 (14) ◽  
pp. 1021-1031
Author(s):  
Dongxu Wang ◽  
Da-Peng Dai ◽  
Hualan Wu ◽  
Jia Chong ◽  
You Lü ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Predictive Power ◽  
Warfarin Dose ◽  
Multivariate Regression Analysis ◽  
Chinese Patients ◽  
Chinese Han ◽  
Dosing Algorithm ◽  
Warfarin Dosing ◽  
Univariate Analyses

Aim: Gene polymorphisms are critical in warfarin dosing variation. Here, the role of rare CYP2C9 alleles on warfarin doses in Chinese Han patients was investigated. Methods: A retrospective study recruited 681 warfarin treated atrial fibrillation patients. The genetic and clinical data were collected. Dose-related variables were selected by univariate analyses and the warfarin-dosing algorithm was derived by multivariate regression analysis. Results: Three rare CYP2C9 alleles ( CYP2C9*13, *16 and *60) were associated with lower stable doses. Inclusion of the rare CYP2C9 alleles in the prediction model added an extra 3.7% warfarin dose predictive power. Conclusion: CYP2C9*13, *16 and *60 was associated with lower stable warfarin doses in Chinese patients. The algorithm including rare CYP2C9 alleles tends to more accurately predict stable warfarin doses.

Warfarin Dosing and Outcomes in Chronic Kidney Disease: A Closer Look at Warfarin Disposition

2019 ◽  
Vol 20 (8) ◽  
pp. 633-645
Author(s):  
Osama Y. Alshogran
Keyword(s):  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Warfarin Therapy ◽  
Oral Anticoagulants ◽  
Cardiovascular Complications ◽  
Efficacy And Safety ◽  
Review Of Literature ◽  
Growing Body ◽  
Warfarin Dosing

Background: Chronic Kidney Disease (CKD) is a prevalent worldwide health problem. Patients with CKD are more prone to developing cardiovascular complications such as atrial fibrillation and stroke. This warrants the use of oral anticoagulants, such as warfarin, in this population. While the efficacy and safety of warfarin in this setting remain controversial, a growing body of evidence emphasizes that warfarin use in CKD can be problematic. This review discusses 1) warfarin use, dosing and outcomes in CKD patients; and 2) possible pharmacokinetic mechanisms for altered warfarin dosing and response in CKD. Methods: Structured search and review of literature articles evaluating warfarin dosing and outcomes in CKD. Data and information about warfarin metabolism, transport, and pharmacokinetics in CKD were also analyzed and summarized. Results: The literature data suggest that changes in warfarin pharmacokinetics such as protein binding, nonrenal clearance, the disposition of warfarin metabolites may partially contribute to altered warfarin dosing and response in CKD. Conclusion: Although the evidence to support warfarin use in advanced CKD is still unclear, this synthesis of previous findings may help in improving optimized warfarin therapy in CKD settings.

Warfarin dosing and cytochrome P450 2C9 polymorphisms

2004 ◽  
Vol 91 (06) ◽  
pp. 1123-1128 ◽  
Author(s):  
F. Johnson ◽  
Janina Longtine ◽  
Nils Kucher ◽  
Hylton Joffe ◽  
Ruliang Xu ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Low Dose ◽  
Pcr Amplification ◽  
Warfarin Dose ◽  
High Dose ◽  
Restriction Enzyme Digestion ◽  
Cytochrome P450 2C9 ◽  
In The Wild ◽  
Warfarin Dosing ◽  
Compound Heterozygotes

SummaryTwo cytochrome P450 2C9 (CYP2C9) polymorphisms, CYP2C9*2 and *3, metabolize warfarin inefficiently. We assessed the extent to which these polymorphisms explain very low warfarin dose requirements and hemorrhagic complications after excluding non-genetic determinants of warfarin dosing. In this retrospective observational study, 73 patients with stable warfarin doses for ≥1 month and International Normalized Ratios (INR) of 2.0–3.0 were enrolled from our Anticoagulation Clinic. Seventeen patients required ≤2 mg (low-dose), 41 required 4–6 mg (moderate-dose), and 15 required ≥10 mg (high-dose) of daily warfarin. CYP2C9 genotyping was assessed by PCR amplification and restriction enzyme digestion analysis of DNA isolated from circulating leukocytes. The CYP2C9 polymorphisms independently predicted low warfarin requirements after adjusting for Body Mass Index, age, acetaminophen use, and race (OR 24.80; 95% CI 3.83–160.78). At least one polymorphism was present in every patient requiring ≤1.5 mg of daily warfarin, and 88%, 37%, and 7% of the low-, moderate-, and high-dose groups, respectively. All homozygotes and compound-heterozygotes for the variant alleles were in the low-dose group. Rates of excessive (INR>6.0) anticoagulation (and bleeding) were 4.5 (6.0), 7.9 (7.9), and 14.7 (0) per 100 patient-years in the wild-types, heterozygotes, and compound heterozygotes/homozygotes, respectively. In conclusion, CYP2C9*2 or *3 compound heterozygotes and homozygotes have low warfarin requirements even after excluding liver disease, excessive alcohol or acetaminophen consumption, low body weight, advancing age, and drug interactions. These polymorphisms increase the rate of excessive anticoagulation, but this risk does not appear to be associated with higher bleeding rates when anticoagulation status is closely monitored.

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