Abstract TMP106: Validation Of The Factors Affecting Basal And Fluctuating Warfarin Doses In The Same Individual Throughout The Year In Japanese Patients
Background: Vitamin K epoxide reductase (VKORC1) and cytochrome p450 isoform (CYP2C9) genotypes contribute to basal therapeutic warfarin doses. Although safe introduction of warfarin is possible, prothrombin time-international normalized ratio (PT-INR) fluctuations requiring continuous adjustment of warfarin doses have been observed in the same patient. Of late, nongenetic factors, in particular renal function, have been associated with warfarin maintenance dose and decreased anticoagulation stability; however, the mechanism of decreased anticoagulation stability has not been identified. This study aimed to elucidate the factors that affect basal and fluctuating warfarin maintenance doses.
Methods: This study was a prospective, multicenter, observational study. Patients who were prescribed warfarin for thromboembolism were enrolled. Patient characteristics and CYP2C9 and VKORC1 genotypes were recorded. To evaluate anticoagulation stability and patient management, we measured PT-INR, estimated creatinine-based GFR (eGFR), and vitamin K intake and examined the warfarin maintenance doses and requirement of warfarin dose change four times a year (seasonally). Vitamin K intake was assessed by a semi-quantitative food frequency questionnaire. Multivariate logistic regression analysis was used to determine the factors affecting basal warfarin doses and PT-INR fluctuations or the necessity of adjustment of warfarin dose.
Results: We analyzed the data of 327 patients. Genotyping results of CYP2C9 and VKORC1 showed that 80% patients had wild type CYP2C9 and the AA genotype of VKORC1. eGFR was 63.2 ± 18.0 ml/min/1.73 m2. Vitamin K intake was 100.0 ± 60.9 μg/day in spring, 91.5 ± 53.8 μg/day in summer, 98.5 ± 69.1 μg/day in autumn, and 108.3 ± 67.0 μg/day in winter. Multivariate analysis showed that age, body surface area, eGFR, and genetic subtypes affected basal warfarin maintenance dose (p < 0.05). Furthermore, except seasonal variation in vitamin K intake, no other factor affected PT-INR fluctuation or the necessity of adjustment of warfarin dose.
Conclusion: Age, body surface area, eGFR, and genetic subtypes affected basal maintenance warfarin dose; however, except vitamin K intake, no other factor affected warfarin dose fluctuation.
- © 2012 by American Heart Association, Inc.