Warfarin has been used as anticoagulant for the long-term treatment of thromboembolic disease, however, the wide spread use is limited by a wide inter-individual variation in dose requirement. Recent studies have demo...Warfarin has been used as anticoagulant for the long-term treatment of thromboembolic disease, however, the wide spread use is limited by a wide inter-individual variation in dose requirement. Recent studies have demonstrated that amiodarone may interact with warfarin to potentiate the anticoagulant effects and lead to an elevated international normalized ratio（INR）. In addition, genetic variation in the vitamin K epoxide reductase complex subunit 1（VKORC1） and cytochrome P450 2C9（CYP2C9） may also affect the dose of warfarin in single or combination therapy. In our study, we aim to examine the effect of amiodarone on the warfarin in different CYP2C9 and VKORC1 status. From September 2008 to November 2009, 207 patients from Beijing, China were enrolled in our study, including 34 patients on combination therapy of amiodarone and warfarin and 173 patients on warfarin therapy. VKORCl and CYP2C9 genotypes were examined using ligation detection reaction（LDR） method. We compared the stable dosage of warfarin and INR between patients on warfarin therapy and patients on warfarin-amiodarone therapy when they are stratified with VKORC1 or CYP2C9 genotype. We did not observe significant difference in dosage or INR between these two groups. The difference in characteristics between these two groups, the blood collection time after amiodarone administration and the method for monitoring may all contribute to the negative finding. Large studies taking into account of these factors are needed to improve our understanding of the interaction between warfarin and amiodarone, as well as the effect of genotype in such interaction.展开更多
Oral anticoagulation therapy with warfarin is used to prevent and treat venous and arterial thrombosis and embolism. Its narrow therapeutic index should be monitored carefully in order to reach the desired outcomes. T...Oral anticoagulation therapy with warfarin is used to prevent and treat venous and arterial thrombosis and embolism. Its narrow therapeutic index should be monitored carefully in order to reach the desired outcomes. The complexity of the pharmacokinetic and pharmacodynamics profile of warfarin makes it a challenge to use during treatment. Its manufacturing characteristics play a key role in its dosage. The aim of this study is to examine and evaluate the effect of two different warfarin regimens in Chinese patients. A cross-sectional study design was adopted. Medical records of all patients （n = 368） who received warfarin therapy in cardio-thoracic surgery wards between Sep. 2008 and Dec. 2009 were reviewed. Details of antithrombotic results of international normalized ratio （INR） monitoring were obtained. Statistical analysis was performed to assess factors predictive of INR therapeutic range at patients＇ discharge time according to different warfarin regimens （2.5 mg in China and 3.0 mg in USA）. The patients＇ mean age was （48.23~12.96） years. The percentage of patients within the INR therapeutic range in the group treated with 2.5 mg warfarin （35.17%） was much lower than that in group treated with 3.0 mg warfarin （47.72%）. Therefore, a significance difference was observed （P = 0.032〈0.05）. In this study, statistical values have shown that most of the patients were related to medical case requesting INR target range of 1.8-2.2 and 2.0-2.5, respectively. There was a statistically significant difference between the two groups. The study showed that the 2.5 mg-warfarin regimen was less suitable than the 3.0 mg-warfarin regimen. Medication regimen should be simplified as much as possible, especially during different treatment period.展开更多
VKORC1 and CYP2C9 have been shown to be strongly associated with Warfarin dosing. However, it is still unclear whether other common genetic variants also contribute to the variation in Warfarin dosing. In the present ...VKORC1 and CYP2C9 have been shown to be strongly associated with Warfarin dosing. However, it is still unclear whether other common genetic variants also contribute to the variation in Warfarin dosing. In the present study, we aim to investigate possible effects of single nucleotide polymorphisms （SNPs） in other candidate genes （CYP4F2, CACNAIC and STX4）, as well as several factors, on stable daily Warfarin dosage （DWMD） in Chinese cardiovascular disease patients. 207 cardiovascular disease patients treated with Warfarin were recruited from Beijing Hospital. DNA was extracted from the blood samples collected one day after Warfarin administration. Nine SNPs （i.e. rs9923231, rs9934438, rs7294, rs1799853, rs1057910, rs4086116, rs2108622, rs216013 and rs10871454 in five genes （i.e. VKORC1, CYP2Cg, CYP4F2, CACNA1C and STX4） were analyzed using ligase detection reactions （LDR）. Univariate analyses and multiple linear regression analyses were performed to analyze the associations between SNPs and other factors （i.e. body surface area （BSA）, Statin medication） and DWMD. Four SNPs （i.e. rs9923231, rs9934438, rs7294 in VKORC1 and rsi0871454 in STX4） had significant statistically effects on DWMD. The multiple linear regression model showed that rs10871454 in STX4, BSA, statin medication, and rs1057910 in CYP2C9 were the significant independent covariates of DWMD. SNP （rs10871454） in STX4 had the strongest effect on Warfarin dosing among the examined candidate genes, indicating that it might serve as a key genetic factor for prediciting the Warfarin maintenance dose in Chinese patients.展开更多
基金The Research Special Fund for Public WelfareIndustry of Health(Grant No.200902008)
文摘Warfarin has been used as anticoagulant for the long-term treatment of thromboembolic disease, however, the wide spread use is limited by a wide inter-individual variation in dose requirement. Recent studies have demonstrated that amiodarone may interact with warfarin to potentiate the anticoagulant effects and lead to an elevated international normalized ratio（INR）. In addition, genetic variation in the vitamin K epoxide reductase complex subunit 1（VKORC1） and cytochrome P450 2C9（CYP2C9） may also affect the dose of warfarin in single or combination therapy. In our study, we aim to examine the effect of amiodarone on the warfarin in different CYP2C9 and VKORC1 status. From September 2008 to November 2009, 207 patients from Beijing, China were enrolled in our study, including 34 patients on combination therapy of amiodarone and warfarin and 173 patients on warfarin therapy. VKORCl and CYP2C9 genotypes were examined using ligation detection reaction（LDR） method. We compared the stable dosage of warfarin and INR between patients on warfarin therapy and patients on warfarin-amiodarone therapy when they are stratified with VKORC1 or CYP2C9 genotype. We did not observe significant difference in dosage or INR between these two groups. The difference in characteristics between these two groups, the blood collection time after amiodarone administration and the method for monitoring may all contribute to the negative finding. Large studies taking into account of these factors are needed to improve our understanding of the interaction between warfarin and amiodarone, as well as the effect of genotype in such interaction.
文摘Oral anticoagulation therapy with warfarin is used to prevent and treat venous and arterial thrombosis and embolism. Its narrow therapeutic index should be monitored carefully in order to reach the desired outcomes. The complexity of the pharmacokinetic and pharmacodynamics profile of warfarin makes it a challenge to use during treatment. Its manufacturing characteristics play a key role in its dosage. The aim of this study is to examine and evaluate the effect of two different warfarin regimens in Chinese patients. A cross-sectional study design was adopted. Medical records of all patients （n = 368） who received warfarin therapy in cardio-thoracic surgery wards between Sep. 2008 and Dec. 2009 were reviewed. Details of antithrombotic results of international normalized ratio （INR） monitoring were obtained. Statistical analysis was performed to assess factors predictive of INR therapeutic range at patients＇ discharge time according to different warfarin regimens （2.5 mg in China and 3.0 mg in USA）. The patients＇ mean age was （48.23~12.96） years. The percentage of patients within the INR therapeutic range in the group treated with 2.5 mg warfarin （35.17%） was much lower than that in group treated with 3.0 mg warfarin （47.72%）. Therefore, a significance difference was observed （P = 0.032〈0.05）. In this study, statistical values have shown that most of the patients were related to medical case requesting INR target range of 1.8-2.2 and 2.0-2.5, respectively. There was a statistically significant difference between the two groups. The study showed that the 2.5 mg-warfarin regimen was less suitable than the 3.0 mg-warfarin regimen. Medication regimen should be simplified as much as possible, especially during different treatment period.
文摘VKORC1 and CYP2C9 have been shown to be strongly associated with Warfarin dosing. However, it is still unclear whether other common genetic variants also contribute to the variation in Warfarin dosing. In the present study, we aim to investigate possible effects of single nucleotide polymorphisms （SNPs） in other candidate genes （CYP4F2, CACNAIC and STX4）, as well as several factors, on stable daily Warfarin dosage （DWMD） in Chinese cardiovascular disease patients. 207 cardiovascular disease patients treated with Warfarin were recruited from Beijing Hospital. DNA was extracted from the blood samples collected one day after Warfarin administration. Nine SNPs （i.e. rs9923231, rs9934438, rs7294, rs1799853, rs1057910, rs4086116, rs2108622, rs216013 and rs10871454 in five genes （i.e. VKORC1, CYP2Cg, CYP4F2, CACNA1C and STX4） were analyzed using ligase detection reactions （LDR）. Univariate analyses and multiple linear regression analyses were performed to analyze the associations between SNPs and other factors （i.e. body surface area （BSA）, Statin medication） and DWMD. Four SNPs （i.e. rs9923231, rs9934438, rs7294 in VKORC1 and rsi0871454 in STX4） had significant statistically effects on DWMD. The multiple linear regression model showed that rs10871454 in STX4, BSA, statin medication, and rs1057910 in CYP2C9 were the significant independent covariates of DWMD. SNP （rs10871454） in STX4 had the strongest effect on Warfarin dosing among the examined candidate genes, indicating that it might serve as a key genetic factor for prediciting the Warfarin maintenance dose in Chinese patients.
