Document Detail


The influence of genetic polymorphisms and interacting drugs on initial response to warfarin in Chinese patients with heart valve replacement.
MedLine Citation:
PMID:  21318593     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE: Compared with genetic factors, drug interactions were largely unexplored in warfarin pharmacogenetic studies. This study sought to systematically investigate the effects of genetic polymorphisms of VKORC1, STX4A, CYP2C9, CYP3A4, and GGCX and interacting drugs on the initial responses to warfarin in Chinese patients with heart valve replacement (HVR). METHODS: A retrospective study was conducted in 809 patients starting warfarin therapy after HVR. The relationships between 12 polymorphisms plus 47 drugs and primary outcomes of the time to the first international normalized ratio (INR) ≥ 1.8 and the time to the first INR > 3.5 and the secondary outcomes of the proportion of time INR < 1.8, the proportion of time INR > 3.5, and the daily warfarin dose in the first 28 days after the initiation of warfarin treatment were analyzed. RESULTS: Genetic polymorphisms and interacting drugs could significantly affect the primary and secondary outcomes. The time to the first INR ≥ 1.8 was significantly influenced by the body surface area (BSA), VKORC1 g.3588G > A allele, and CYP2C9*3 allele, with hazard ratio (HR; 95% confidence interval [CI]) of 0.34 (0.17-0.66), 2.71 (2.2-3.35) and 1.43 (1.07-1.93) respectively. The time to the first INR > 3.5 was affected not only by BSA, VKORC1 g.3588G > A allele, and CYP2C9*3 allele with HR (95%CI) of 0.26 (0.07-0.99), 2.76 (1.61-4.72), and 3.09 (2.02-4.74) respectively, but also by age and interacting drugs, including fluconazole, amiodarone, and simvastatin with HR (95%CI) of 1.02 (1.01-1.04), 2.66 (1.16-6.08), 1.78 (1.17-2.73), and 5.33 (1.67-16.96) respectively. CONCLUSIONS: Not only VKORC1 and CYP2C9 genotypes, but also interacting drugs, had a significant impact on the variability of the initial response to warfarin.
Authors:
Shi-Long Zhong; Yuan Liu; Xi-Yong Yu; Dan Xu; Hong-Hong Tan; Qiu-Xiong Lin; Min Yang; Hai-Yan Lao; Shu-Guang Lin
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-12
Journal Detail:
Title:  European journal of clinical pharmacology     Volume:  -     ISSN:  1432-1041     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-2-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1256165     Medline TA:  Eur J Clin Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Guangdong Provincial Cardiovascular Institute, Medical Research Center of Guangdong General Hospital, Guangdong Institute of Clinical Pharmacology, Guangdong Academy of Medical Sciences, 96 Dongchuan Road, Guangzhou, GD, 510080, People's Republic of China.
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