Anticoagulant Therapy in Japanese Patients With Mechanical Mitral Valves.

Matsuyama, Katsuhiko; Matsumoto, Masahiko; Sugita, Tadaaki; Nishizawa, Junichiro; Yoshida, Kazunori; Tokuda, Yoshiyuki; Matsuo, Takaaki

doi:10.1253/circj.66.668

Cited by 44 publications

(29 citation statements)

References 15 publications

(11 reference statements)

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“…1,29) Significance and applications in dental surgery: Continuous oral anticoagulant therapy with warfarin has been used to decrease the risk of thromboembolism for more than half a century. The recent guidelines for anticoagulant therapy recommend that interrupting warfarin treatment for dental or minor surgery is prohibited (class III on guideline).…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of Combined CYP2C9 and VKORC1 Genotypes in Japanese Patients Requiring Warfarin

2011

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SummaryThe individual management of anticoagulation therapy is important for safe medical outcomes, including those of oral surgery. Here, Japanese patients who received warfarin (n = 35) and normal controls (n = 125) were analyzed by real-time PCR to determine the frequencies of single nucleotide polymorphisms in VKORC1 (vitamin K epoxide reductase complex, subunit 1) and CYP2C9 and how these frequencies related to warfarin dose and PT-INR. The genetic polymorphisms CYP2C9 *2 (416 C > T), CYP2C9 *3 (1061 A > C), and intron 1-136 C > T in VKORC1 (1173 C > T) were measured. All patients had the wild-type CYP2C9 gene (*1/*1). All 160 cases had the wild-type (CC) type CYP2C9 *2 , 93.8% had AA type CYP2C9 *3 , 6.2% had AC type CYP2C9 *3 , 1.2% had CC type VKORC1, 13.8% had CT type VKO-RC1, and 85% had TT type VKORC1. The CC type VKORC1 genetic polymorphism was associated with a significantly higher mean warfarin maintenance dose (4.5 ± 0.5 mg) than other VKORC1 genotypes (TT type 2.9 ± 0.1 mg: CT type 3.4 ± 0.3 mg). Categorization of the patients in terms of the combined CYP2C9 and VKORC1 haplotype (the warfarinresponsive index; WRI) revealed the mean daily warfarin maintenance dose was 3.0 ± 0.1 mg for WRI 1 and 3.7 ± 0.3 mg for WRI 2 (P < 0.012). The event survey revealed 2 patients with nonfatal cerebral hemorrhage had a WRI score of 2 (VKORC1 C/T heterozygosity genotype). Thus, CYP2C9 and VKORC1 haplotype analysis allows prediction of warfarin maintenance dosage. The findings may provide a personalized use of warfarin in the field of oral surgery. (Int Heart J 2011; 52: 44-49)

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Section: Discussionmentioning

confidence: 99%

Clinical Significance of Combined CYP2C9 and VKORC1 Genotypes in Japanese Patients Requiring Warfarin

2011

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“…5, 9 Moreover, it has been reported that compared with Europeans, the incidence of thromboembolism is low in Japan, despite the less intensive regimen; 10,11 which indicates that adjusted low-dose warfarin (eg, PT-INR 1.6-2.6) is optimal for prevention of thromboembolism in Japanese patients. 12, 13 Considering these racial differences in the anticoagulation therapy, we attempted to validate the IWPC pharmacogenetic dose algorithm for warfarin in Japanese patients under low-TAKEUCHI F et al…”

Section: Editorial P 850mentioning

confidence: 99%

Evaluation of Pharmacogenetic Algorithm for Warfarin Dose Requirements in Japanese Patients

Takeuchi

Kashida

Okazaki

et al. 2010

Circ J

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Background: Warfarin dosing is difficult to establish because of considerable interindividual variation. Thus, warfarin pharmacogenetics have attracted particular interest in relation to appropriate control of anticoagulation. Methods and Results:The 200 eligible subjects were chosen from participants in a hospital cohort. Performance of a pharmacogenetic algorithm recently developed by the International Warfarin Pharmacogenetics Consortium (IWPC) was tested and compared with a clinical algorithm (without genotype data) by calculating the percentage of patients for whom the predicted dose deviated by less than 7 mg/week (1 mg/day) from the actual dose. The pharmacogenetic algorithm accurately identified a significantly (P<0.05) larger proportion of patients to achieve the target international normalized ratio than did the clinical algorithm (68% vs 36% for a low-dose group; and 21% vs 0% for a high-dose group). Also, an increase in warfarin dosage was found to be appropriate for the current status of alcohol drinking (4 mg/week, as against non-drinking) and smoking (3.3 mg/week, as against non-smoking). Conclusions:The IWPC pharmacogenetic algorithm has clinical application, particularly in identifying Japanese patients who require a low dosage of warfarin and are at greater risk of excessive anticoagulation. (Circ J 2010; 74: 977 - 982)

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“…The maintenance dose of warfarin is usually determined by monitoring prothrombin time using an international normalization ratio (INR). An INR of 1.5-2.5 is recommended for Asian populations (Matsuyama et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Association of VKORC1 and CYP2C9 polymorphisms with warfarin dose requirements in Japanese patients

et al. 2006

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Warfarin is the most commonly used oral anticoagulant for treatment of thromboembolism, but adjustment of the dose appropriate to each patient is not so easy because of the large inter-individual variation in dose requirement. We analyzed single nucleotide polymorphism (SNP) genotypes of the VKORC1 and CYP2C9 genes using DNA from 828 Japanese patients treated with warfarin, and investigated association between SNP genotype and warfarin-maintenance dose. Five SNPs in VKORC1, 5¢ flankingÀ1413A>G, intron 1À136T>C, intron 2+124C>G, intron 2+837T>C and exon 3 343G>A, were in absolute linkage disequilibrium, and showed a significant association with daily warfarin dose of these patients. The median warfarin dose of patients with homozygosity for the minor allele was 4.0 mg/day, which is significantly higher than those heterozygous for the minor allele (3.5 mg/day) or those homozygous for the major allele (2.5 mg/day; P=5.1·10 À11 in the case of intron 1À136T>C SNP). We then genotyped the CYP2C9 gene for the Japanese common genetic variant, CYP2C9*3 and, based on the genotype of these two genes, classified patients into three categories, which we call ''warfarin-responsive index.'' The median warfarin daily dose varied significantly in this classification according to the warfarin-responsive index (2.0 mg/day for index 0 group, 2.5 mg/day for index 1 group, and 3.5 mg/day for index 2 group; P=4.4·10 À13 ). Thus, analysis of the combination of VKORC1 and CYP2C9 genotypes should identify warfarin-sensitive patients who require a lower dose of drug, allowing personalized warfarin treatment.

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Anticoagulant Therapy in Japanese Patients With Mechanical Mitral Valves.

Cited by 44 publications

References 15 publications

Clinical Significance of Combined CYP2C9 and VKORC1 Genotypes in Japanese Patients Requiring Warfarin

Clinical Significance of Combined CYP2C9 and VKORC1 Genotypes in Japanese Patients Requiring Warfarin

Evaluation of Pharmacogenetic Algorithm for Warfarin Dose Requirements in Japanese Patients

Association of VKORC1 and CYP2C9 polymorphisms with warfarin dose requirements in Japanese patients

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