Patient Factors against Stable Control of Warfarin Therapy for Japanese Non-valvular Atrial Fibrillation Patients

Tomita, Hideharu; Kadokami, Toshiaki; Momii, Hidetoshi; Kawamura, Natsumi; Yamaguchi, Masayoshi; Inou, Tetsuji; Fukuizumi, Yutaka; Usui, Makoto; Funakoshi, Kouta; Yamada, Satoshi; Aomori, Tohru; Yamamoto, Koujiro; Uno, Tsukasa; Ando, Shin Ichi

doi:10.1016/j.thromres.2013.09.003

Cited by 18 publications

(24 citation statements)

References 17 publications

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“…Second, pharmacogenomics of warfarin metabolism such as VKORC1 and CYP2C9 polymorphisms were not considered. With respect to this concern, Tomita et al 32) reported that these polymorphisms affect dose but not stability of warfarin therapy in Japanese patients with NVAF. Third, the present study should have added more comprehensive baseline characteristics including socioeconomics as in the other studies 20, 33) .…”

Section: Discussionmentioning

confidence: 99%

Anticoagulation Stability Depends on CHADS<sub>2</sub> Score and Hepatorenal Function in Warfarin-treated Patients, Including Those with Atrial Fibrillation

Odashiro

Yamaguchi

Fukata

et al. 2017

JAT

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Aim: Although warfarin remains important despite the widespread use of nonvitamin K antagonist oral anticoagulants (NOACs), to date, the reality of warfarin use in the “NOACs era” is unclear. This multicenter observational study aimed to clarify the key factors contributing to warfarin treatment stability.Methods: The practical use of warfarin, stability of warfarin therapy, and factors contributing to this stability were investigated in community-based hospitals through a real-world study. Clinical data were retrospectively extracted from the medical records of warfarin-treated Japanese patients (age, 71.3 ± 5.5 years) with atrial fibrillation (AF), prosthetic heart valve, or other concerns requiring anticoagulation. Treatment stability was considered as time in therapeutic range of international normalized ratio of prothrombin time (TTR: %). The factors contributing to TTR were investigated, including CHADS2 score components.Results: Mean CHADS2 score was highest (1.38 ± 0.88, p < 0.001), and most CHADS2 score components in addition to hepatorenal dysfunction were factors contributing to the low TTR in patients with AF (n = 176). The similarity was found in overall patients who were prescribed warfarin (n = 518). TTR decreased according to the CHADS2 score component accumulation. Gender, dose and prescription interval of warfarin, and co-administration of antiplatelet agents did not correlate with the low TTR.Conclusions: This retrospective study demonstrated that the CHADS2 score component accumulation and hepatorenal dysfunction are factors significantly contributing to the low TTR, which is indicative of poor warfarin treatment stability, in patients such as those with AF.

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Section: Discussionmentioning

confidence: 99%

Anticoagulation Stability Depends on CHADS<sub>2</sub> Score and Hepatorenal Function in Warfarin-treated Patients, Including Those with Atrial Fibrillation

Odashiro

Yamaguchi

Fukata

et al. 2017

JAT

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“…While other studies found a significant association between stability and age 33 . There are differences related to anticoagulants efficacy, especially among women, as it was found that female gender significantly spend more time outside the INR therapeutic range than men, as shown in a recently published study, 29% of women where below the INR therapeutic range versus 26% of men, by this putting them at a more risk of ischemic stroke 34 . In our study, INR values were of therapeutic stability in 42.9% of females among stable group versus 65% of males.…”

Section: Non-genetic Factorsmentioning

confidence: 94%

Genetic and Non-Genetic Factors Association with Warfarin Long Term Therapy Stability in Sudan

Aldahab¹,

Elkhawad²

2016

AJPRHC

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Anticoagulation with warfarin is characterized by a wide inter-individual variations in dose requirements and INR (International Normalised Ratio) stability, as there are evidences that warfarin response variability is associated with CYP2C9 (cytochrome P450, family 2, subfamily C, polypeptide 9) and VKORC1 (Vitamin K epoxide reductase complex1) genetic polymorphisms. Carriers of CYP2C9*2 and VKORC11639G>A variant alleles are at greater risk of unstable anticoagulation therapy. Objectives: This retrospective case control study was directed to analyze the impact of genetic and non-genetic factors on warfarin therapy in Sudanese out-patients who were on long term warfarin therapy. Method: 118 Sudanese outpatients receiving warfarin treatment for at least six months, were interviewed for their non-genetic factors that included age, sex, indication for warfarin therapy, compliance, Vitamin K rich foods intake and concomitant drug therapy, in addition to their blood samples which were taken for DNA extraction and genotyping of CYP2C9*2 and VKORC11639G>A gene polymorphisms to study the genetic factors. INR stability % index was calculated, accordingly patients were classified into 2 groups, stable and unstable groups. Results: The frequencies of VKORC11639G>A alleles in Sudanese out-patients who were on long term warfarin therapy were 70.3% and 29.7% for the VKORC1/G and VKORC1/A alleles respectively. The frequencies of CYP2C9*2 alleles in Sudanese out-patients were 92.4% and 7.6% for CYP2C9*1 and CYP2C9*2 alleles respectively. Variables associated with low INR stability were VKCOR1/AA genotype (p-value = 0.028) and sex (p = 0.017). Variables that showed no association with INR stability were age (p-value = 0.259), compliance (p-value = 0.058). Vitamin K rich foods intake (p-value = 0.743), and mean stable warfarin dose (p-value = 0.439). Conclusion: Polymorphism in warfarin drug target gene VKORC1-11639G>A and sex are important elements of INR stability in Sudanese out-patients on long term warfarin therapy.

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“…5, 23 One possible mechanism may be unstable drug metabolism via liver dysfunction caused by congestive liver and/or renal dysfunction from the use of diuretics by patients with symptomatic HF, although it is not assumed there are so many outpatients in such an unstable state. Similarly, polypharmacy is often seen in patients with HF, especially those with a greater number of comorbidities, which would substantially modify the pharmacokinetics.…”

Section: Predictors Of High Inr Variabilitymentioning

confidence: 99%

Predictors of International Normalized Ratio Variability in Patients With Atrial Fibrillation Under Warfarin Therapy

Yoshimi

Suzuki

Arita

et al. 2018

Circ J

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Background: Variability in the international normalized ratio (INR) of prothrombin time has been suggested to be related to outcome in patients with atrial fibrillation (AF) under warfarin therapy, but its determinants remain unclear. Methods and Results:The study population consisted of 626 AF patients under warfarin therapy in the Shinken Database (n=22,230). INR variability was calculated by Fihn's method. Determinants of high log INR variability (defined as over mean+standard deviation) were determined by logistic regression analyses. Symptomatic heart failure (odds ratio [OR] 3.974, 95% confidence interval [CI] 2.510-6.292), older age (≥75 years old; OR 2.984, 95% CI 1.844-4.826) and severe renal dysfunction (eGFR <30 mL/min/1.73 m 2 ; OR 3.918, 95% CI 1.742-8.813) were identified as independent predictors of high INR variability on multivariate logistic regression analysis. Conclusions:The determinants of INR variability in AF patients under warfarin therapy could assist Japanese clinicians in identifying patients likely to show unstable warfarin control irrespective of the definition of the target INR range.

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Patient Factors against Stable Control of Warfarin Therapy for Japanese Non-valvular Atrial Fibrillation Patients

Cited by 18 publications

References 17 publications

Anticoagulation Stability Depends on CHADS<sub>2</sub> Score and Hepatorenal Function in Warfarin-treated Patients, Including Those with Atrial Fibrillation

Anticoagulation Stability Depends on CHADS<sub>2</sub> Score and Hepatorenal Function in Warfarin-treated Patients, Including Those with Atrial Fibrillation

Genetic and Non-Genetic Factors Association with Warfarin Long Term Therapy Stability in Sudan

Predictors of International Normalized Ratio Variability in Patients With Atrial Fibrillation Under Warfarin Therapy

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