| Objective:To evaluate warfarin INR—based efficacy and safety in the patients who need anticoagulation treatment by multivariable regression equation or tradition predition for warfarin dosage.Methods:Consenting patients(n=125) were randomized to a individulized group(n=58) and trditional group(n=67).Every patients' a international normalized ratio(INR) of the prothrombin time(PT) was within range 2.0-3.0.Patients' age,sex,height,weight and INR were collected.The patients in the individulized group were given warfarin dosage predicted by a multivariable regression equation including the VKORC1(-1639G＞A),CYP2C9 genotype,age and weight,D=6.22-0.011(Age) + 0.017(Weight) -0.775(CYP*3)-3.397(VKORC1-x1)-4.803(VKORC1-x2),whereas the traditional group of warfarin dosing followed a clinical empirical protocol.Prothrombin time(PT)international normalized ratio(INR) was measured routinely on days 0,3,5,8,15,30,60。All patients were followed up for 2 months.PCR-RFLP method were used for the detection of VKORC1(-1639G＞A) and CYP2C9 genotype.Results:1.According to warfarin dosage needed in the different genotype patients,dosage requiements were higher in VKORC1(-1639G＞A) GA+GG phenotype than that in AA type(17.60±3.58 mg/wk vs 12.91±5.10 mg/wk,p=0.001).For the CYP2C9 phenotype, dosage requirement is higher in * 1/* 1 type than that in * 1/*3(14.67±4.79 mg/wk vs 9.77±2.03 mg/wk,p=0.006).These results further validated our former study.2.The initial warfarin dosage by using dosing algorithms in the individulized group were more closer to the stable dose than traditional group(P＜0.001).Its dose adjustments per patient were 0.46±0.33mg,whereas the traditional group of dose adjustments were 0.95±0.41mg,which were significantly difference(p=0.002).It showed that individulized group was more closer to stable dose,resulting in smaller and fewer dosing adjustment.3.The percentage of out-of-range target INR for the the individulized group whose initial warfarin dosage was followed by multivariable regression equation was 25.9±5.8%,whereas the traditional group,the percentage out-of-range target INR is 41.8±6.0%,it decreased 15.9±0.2%(p<0.05).It suggested that the more and more patients can directly achieve target INR followed multivariable regression equation in patients who need anticoagulation therapy.4.For the duration to get target INR range,it was 7.06±3.15 days in the individulized. group,and 10.58±5.11 days in traditional group.About 3.52±1.96 days(P=0.002) in advance in the individulized group.It can indicated that the patients who get initial dosage using dosing algorithms can get target INR range in advance.5.As to clinical adverse events incidence rate in the two groups,the individulized group was 3.4±2.4%,and the traditional group was 14.9±4.4%,decreasing 11.5±2.0%(p =0.0298) in the individulized group.Whereas,as to risk of an INR higher than 4,the individulized group was 5.2±2.9%,and the traditional group was 19.3±4.8%,decreasing 14.1±1.9%(P=0.0176) in the individulized group.It indicated that the individulized group could decrease warfarin adverse event rate.Conclusions:Warfarin dosing by a multivariable regression equation in patients could increase efficiency for warfarin dose adjustment,and also could decrease warfarin adverse event.We concluded that the multivariable regression equation could give suggestion for the individualization and rationalization for warfarin.
|
PDF Full Text Request