1.
Impact of genetic and clinical factors on warfarin therapy in patients early after heart valve replacement surgery.
Li, B, Liu, R, Wang, C, Ren, C, Zhang, S, Zhang, F, Zhang, J, Liu, S, Wei, Y, Liu, W, et al
European journal of clinical pharmacology. 2019;(12):1685-1693
Abstract
PURPOSE Factors influencing responsiveness to warfarin at treatment onset time were not well identified in Chinese patients undergoing heart valve replacement. We sought to select the most relevant factors that associated with patient response to warfarin early after heart valve surgery. METHODS In this observational study, 289 patients starting warfarin therapy early after heart valve replacement surgery were enrolled. CYP2C9 *1, *2, *3, and *5; VKORC1-1639 G>A, CYP4F2 V433M, and GGCX rs11676382 genotypes; clinical characteristics, response to therapy, and bleeding and thrombosis events were collected. The primary outcomes were the time to the first INR equal to or more than lower limit of therapeutic range and the warfarin dose requirements. Stepwise multiple linear regression was performed to develop a dosing algorithm to predict the warfarin dose requirements. RESULTS The results of univariate analysis showed lone VKORC1-1639 G>A, CYP2C9 *1/*3, cefazolin, cefoperazone-sulbactam, increased BMI, Δhemoglobin, and white blood cell count could significantly affect patient responsiveness to warfarin in the initial period of anticoagulation. Multivariate analysis resulted in an equation: Accumulated warfarin doses (mg) = 17.068 VKORC1-1639 G>A - 4.261 hypertension + 0.593 BMI - 0.115 age - 4.852 CYP2C9 *1/*3 - 2.617 cefazolin - 4.902 cefoperazone-sulbactam - 4.537, which could explain 40.2% of the variability in warfarin dose needed to reach the first INR equal to or more than lower limit of therapeutic range. CONCLUSIONS Both genetic and clinical factors contributed to anticoagulation effect of warfarin in the initial period of treatment. Our findings could provide a basis for the personalized management of warfarin use in the early stage of anticoagulation in northern Chinese patients.
2.
[A randomized controlled study of the VKORC1 and CYP2C9 genotypes in guiding warfarin therapy for pulmonary thromboembolism].
Li, J, Liu, S, Yang, JH, Guo, W, Wang, ZZ, Chen, Y, Wang, SH
Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases. 2013;(12):950-3
Abstract
OBJECTIVE To evaluate the clinical application of a dosing algorithm by genotypes in prediction of warfarin maintenance dose in Chinese patients with pulmonary thromboembolism. METHOD During October 2010 and August 2012, 220 inpatients or outpatients with pulmonary embolism in Beijing Anzhen Hospital, were enrolled by the inclusion criteria. The patients included 86 males and 134 females. The clinical data and blood samples were collected. The fluorescent PCR genotyping method was used to detect the genotypes of vitamin K epoxy compounds reductase complex subunit 1 (VKORC1) and cytochrome P450 enzyme 2C9 (CYP2C9). According to the random number table, the patients were randomly divided into a study group and a control group. In the study group, the first 3 doses of warfarin were prescribed according to the predicted warfarin dose, while in the control group the drug was prescribed according to the dose estimated empirically by clinicians. Warfarin was adjusted until it reached a stable dose according to the INR value, and the following-up lasted for 50 days. RESULT AT the end of follow-up, the percentage of patients who obtained a stable dose in the study group and the control group was 82.1% (n = 78) and 66% (n = 64), respectively. The mean time to reach a stable dose in the study group and the control group was (16.8 ± 1.5) and (25.6 ± 1.8) days, and the median time was (11.0 ± 1.0) days and (20.0 ± 2.0) days, the difference between the 2 groups being statistically significant (χ(2) = 18.175, P < 0.001). The incidence of side effects of the study group was lower than that of the control group, and the time to the occurrence of side effects in study group was longer. The average predicted dose of the 142 patients who reached a stable dose was (3.6 ± 0.9) mg/d, and the average effective dose was (3.7 ± 1.3) mg/d, the average predicted dose being lower than the actual dose (0.1 ± 1.2) mg/d, but the difference was not significant(t = -1.202, P > 0.05). CONCLUSION The warfarin stable dose prediction algorithm, containing genetic factors and non-heritage factors, can significantly shorten the adjustment time to reach warfarin stable dose, and reduce the incidence of side effects, and is clinically applicable.