| Objective: After bioprosthetic valve replacement,patients need warfarin anticoagulation treatment for 6 months,but there is no unified standard for the choice of anticoagulation intensity in China at present.Generally,the international normalized ratio(INR)of such patients is controlled within the range of 1.5～2.2,but some patients still have anticoagulation syndromes.The choice of appropriate anticoagulation intensity for patients after bioprosthetic valve replacement has a significant impact on the clinical outcomes and long-term survival.The study found that individualized anticoagulation therapy can effectively reduce anticoagulation complications,but there are few studies on the influencing factors and weights of anticoagulation intensity selection.In this study,the factors influencing the choice of anticoagulation intensity of warfarin after bioprosthetic heart valve replacement were discussed,and constructed a stable dose model of warfarin in patients after heart valve replacement on this basis to further standardize the range of anticoagulation intensity of warfarin after bioprosthetic heart valve replacement,in order to reduce the occurrence of postoperative anticoagulation complications of such patients,improve clinical efficacy and patient compliance,and provide real-world research evidence for individualized anticoagulation treatment.Methods: Retrospectively analyze the clinical data of 260 patients underwent the heart valve surgery,the fluorescent staining in situ hybridization was used to perform CYP2C9 and VKORC1-1639G>A gene detection,and related factors such as gender,age,genotype were included to influence the stable dose of warfarin,and the weights of the influencing factors were analyzed by multiple linear regression analysis,and on this basis,a stable dose prediction model of warfarin after heart valve surgery was established.In addition,74 patients who met the selection criteria for bioprosthetic heart valve replacement were selected as the observation objects.Patients with INR values ranging from 1.5 to 1.8(including 1.8)were included in the low-intensity anticoagulation group,and patients with INR values ranging from 1.8 to 2.2 were included in the high-intensity anticoagulation group.The patients were followed up for6 months,and the laboratory test results such as blood biochemistry(including white blood cell,cholesterol,etc),blood coagulation routine,cardiac enzyme profile and electrolytes were recorded at the first month,the third month and the sixth month after discharge,and safety monitoring were carried out.The vital signs of patients and the incidence of related adverse events such as bleeding,embolism were recorded,and the corresponding data were statistically analyzed.The precision of the established prediction model was validated by plotting Bland-Altman plots,ideal prediction percentages,and mean absolute error(MAE).Results: Retrospective analysis showed that the daily dose of warfarin for patients with CYP2C9~*3 AA genotype and AC genotype was(2.43±0.79)mg/d and(2.22 ± 0.68)mg/d,there was no statistically significant difference(P>0.05).The daily dose of warfarin for VKORC1-1639 GG genotype patients was(4.11±1.66)mg/d,which was obviously higher than that for AA genotype patients and AG genotype patients(P<0.05).The formula of stable dose of warfarin was obtained by multiple regression analysis:D(mg/d)=2.480-0.017× age +0.617×BSA+0.447×(VKORC1-1639G>A)-0.353×amiodarone-0.745× atrial fibrillation.Prospective analysis showed that the PT,INR and APTT in the high-intensity anticoagulation group were higher than those in the low-intensity anticoagulation group,and the blood calcium test index was lower than that in the low-intensity anticoagulation group,there were statistical difference(P<0.05).In the data of laboratory examination in the third month,the AST in the high-intensity anticoagulation group was lower than that in the low-intensity anticoagulation group,while the PT and INR were significantly higher than those in the low-intensity anticoagulation group,and there were statistical difference(P<0.05).In the laboratory examination data of the sixth month,the PT,INR,total cholesterol and blood sodium in the high-intensity anticoagulation group were higher than those in the low-intensity anticoagulation group,and there were statistical difference(P<0.05).The incidence of adverse events in high-intensity anticoagulation group during the follow-up period was8(20.00%),and that in low-intensity anticoagulation group was 1(2.94%).The incidence of adverse events in low-intensity anticoagulation group was significantly lower than that in high-intensity anticoagulation group(P<0.05).Univariate analysis showed that patients’ time in therapeutic rang and the position of valve replacement were the factors affecting the anticoagulation intensity(P<0.05),and binary Logistic regression showed that patients with TTR>65% were likely to have higher anticoagulation intensity than those with TTR<65% [OR = 4.106,95% CI(1.452 ～11.610)].To verify the accuracy of the model established in the early stage,the ideal prediction percentage of the model is 67.57%,the MAE is(0.50±0.65)mg/d,and the percentage of the actual doses outside the predicted dose of 95% CI is 5.40%.Conclusion: In this study,the stable dose model of warfarin can well calculate the dose of warfarin anticoagulation in patients undergoing bioprosthetic heart valve replacement.For patients undergoing bioprosthetic heart valve replacement,postoperative low-intensity anticoagulation therapy can reduce the occurrence of related adverse effects.And INR value monitoring should be strengthened during the follow-up period and strictly control the range of INR values in patients. |
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