ArticleEuropean journal of clinical pharmacology2011
The influence of genetic polymorphisms and interacting drugs on initial response to warfarin in Chinese patients with heart valve replacement.
Article in European journal of clinical pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 14 citations in OpenAlex.
- [The Effect ofSichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2021Article
- Impact of genetic and clinical factors on warfarin therapy in patients early after heart valve replacement surgery.European journal of clinical pharmacology · 2019Observational
- The effect of CYP2C9 and VKORC1 genetic polymorphisms on warfarin dose requirements in a pediatric population.Anatolian journal of cardiology · 2016Article
- Warfarin dosage adjustment strategy in Chinese population.International journal of clinical and experimental medicine · 2015Article
- Miniature short hairpin RNA screens to characterize antiproliferative drugs.G3 (Bethesda, Md.) · 2013Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeCompared 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).
methodsA 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.
resultsGenetic 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.
conclusionsNot only VKORC1 and CYP2C9 genotypes, but also interacting drugs, had a significant impact on the variability of the initial response to warfarin.
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