Analysis of the Impact Factors on a Stable Warfarin Dose in Extreme Elderly (Age ≥ 80 Years) Chinese Patients with Non-Valvular Atrial Fibrillation

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.