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Abstract
Purpose: The aim of this study was to investigate non-genetic and genetic factors contributing to stable warfarin dose change in the extreme elderly patients with non-valvular atrial fibrillation. Methods: A total of 40 elderly patients with stable warfarin doses were included in this study. Clinical basic data, such as age, sex, body mass index, basic disease like hypertension, diabetes and coronary heart disease had been recorded. Two nucleotide polymorphisms about VKORC1-1639G^A and CYP2C9 1075A^C genes were detected via sequencing by hybridization. Results: The elderly patients with CYP2C9 1075A^C (CA) genotype needed less warfarin daily doses than those with CYP2C9 1075A^C (AA) genotype (1.93 ± 0.79 mg/d VS 2.15 ± 0.64 mg/d), but there was no significant difference (p = 0.601). While the daily warfarin dose required for patients with VKORC1-1639G^A (AA) genotype was significantly lower than that for patients with VKORC1-1639G^A (GA) genotype (2.00 ± 0.67 mg/d VS 2.63 ± 0.38 mg/d, p = 0.012). VKORC1-1639G^A together with age and diabetes status accounted 41.7% for dose variability. The new algorithm was developed using multivariate linear regression analysis; the model was developed for: Dose = 7.731 – 0.056 * age + 0.527 * DM - 0.785 * VKORC1. Conclusions: VKORC1-1639G^A together with age and diabetes status might predict warfarin doses in age ≥ 80 years patients with non-valvularatrial fibrillation. In contrast, the polymorphism of CYP2C9 1075A^C was not associated with dose variability.
Highlights
Non-valvular atrial fibrillation (NVAF) is a common arrhythmia and the disease incidence increases with age
The aim of this study was to investigate non-genetic and genetic factors contributing to stable warfarin dose change in the extreme elderly patients with non-valvular atrial fibrillation
The results showed that age, diabetes history and vitamin K-epoxide reductase (VKORC1) genotype were independent factors influencing the stable daily dose of warfarin (Table 3)
Summary
Non-valvular atrial fibrillation (NVAF) is a common arrhythmia and the disease incidence increases with age. Stroke risk associated with atrial fibrillation increases significantly with age, from only 1.5% in the 50 - 59 years age-group to 23.5% in the 80 - 89 years age-group among patients with NVAF [2]. It is difficult to achieve a stable anticoagulation control because different patients have a great variability of warfarin response [7]. This variability is mainly because of the vitamin K-epoxide reductase (VKORC1) polymorphisms and the cytochrome P450 enzyme gene (CYP2C9) polymorphisms, both of which affect warfarin metabolism [8] [9] [10]. Jia L et al have found that in Chinese population, VKORC1 and CYP2C9 polymorphisms play an important role in warfarin sensitivity [11]
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