Safety And Efficacy Analysis Of Warfarin Precision Anticoagulant Therapy In Patients With Nonvalvular Atrial Fibrillation

Objective:The warfarin gene polymorphism test results were used to guide warfarin anticoagulant therapy in patients with NVAF,and patients were followed up telemedicine.To evaluate the safety and efficacy of warfarin precision anticoagulant therapy under the mode of telemedicine+genetic testing.In this way,accurate anticoagulation of warfarin may be realized,and evidence support can be provided for the rational clinical application of warfarin.Methods:Patients with non-valvular atrial fibrillation who were admitted to the Department of Cardiology of Northern Jiangsu People,s Hospital from September 2018 to January2020.All the enrolled patients joined the telemedicine platform and signed their informed consent.Whether to undergo warfarin genetic testing was decided according to the patient’s wishes,and they were divided into the precise group（genetic testing+telemedicine）and the conventional group（telemedicine）.After receiving warfarin genetic test,the IWPC warfarin dose prediction model was used to calculate the initial dose in the precision group.The conventional group was given initial dose according to clinician’s experience.After receiving warfarin genetic test,the IWPC warfarin dose prediction model was used to calculate the initial dose in the precision group.The conventional group was given initial dose according to clinician’s experience.The INR monitored during patients’follow-up was recorded in detail.The dosage was adjusted according to the INR value.The steady-state dose of warfarin,major bleeding events defined by ISTH（International Thrombosis and Hemostasia Association）,minor bleeding events,INR>3.5,TTR at the different time,INR<1.2,embolic events and other adverse reaction events of the two groups were recorded.Results:A total of 165 patients were included in this study,including 79 patients in the precision group and 86 patients in the conventional group.A total of 164 patients completed the 12-month follow-up,including 79 patients in the precision group（100%）and 85 patients in the conventional group（98.84%）.There were no statistically significant differences in baseline characteristics between the two groups,such as age,gender,body weight,associated diseases,drug combination,initial INR value,CHA₂DS₂-VASc score and HAS-BLED score（P>0.05）.In the precise group,there were 73 cases of wild homozygous AA type（92.41%）and 6 cases of heterozygous AC type（7.59%）according to CYP2C9*3 genotype test results.There were 63 cases of mutant homozygous AA type（79.75%）and 16 cases of heterozygous GA type（20.25%）according to VKORC1 genotype test.The genotype distribution was in accordance with the Hardy-Weinberg genetic balance law.The recommended dose of warfarin calculated by IWPC dose prediction model was（2.63±0.68）mg,and the steady-state dose was（2.62±0.83）mg.The recommended dose of gene detection was basically consistent with the steady-state dose（P>0.05）.Linear correlation analysis was conducted between the recommended dose for genetic testing and the steady-state dose,the correlation coefficient R=0.787（P<0.01）.No major bleeding event occurred in the two groups;Small bleeding events occurred in 4 cases（5.1%）in the precision group and 7 cases（8.2%）in the the conventional group,the difference was not statistically significant（P>0.05）.5 cases（6.3%）of the INR>3.5 occurred in the precision group and 16 cases（18.8%）occurred in the the conventional group,the difference was statistically significant,（P<0.05）.In the precision group of INR>3.5 events,there was one patient with gingival bleeding,and one patient was caused due to taking food at the same time,luckily,the patient did not bleed.In the conventional group of INR>3.5 events,there was three patients complicated with bleeding,one with nosebleed,two with gingival bleeding,and one patient was caused due to taking at the same time,luckily,the patient did not bleed.In the conventional group,there were 3 patients complicated with bleeding,1 with nosebleed,2 with gingival bleeding,and 1 patient with abnormally high INR due to taking cold remedies at the same time,luckily,the patient did not bleed.We compared the average INR of the first five times between the two groups,we found that the INR of the precision group tended to be more stable in the early stage,and the INR fluctuation range between the two groups was significantly different at the beginning of anticoagulation.The TTR of the precision group in the first 1,3 and 6 months were（73.8±17.8）%,（77.8±8.5）%,（77.1±7.3）%,respectively,and the TTR of the conventional group in the first 1,3 and 6 months were（67.7±15.2）%,（73.1±10.9）%,（75.5±9.1）%,respectively.The difference of TTR between the two groups in the first one and three months was statistically significant（P<0.05）.The TTR of the precision group was still higher than that of the conventional group in the first six months,but the difference was not statistically significant.There were 1 case and 2 cases of cerebral embolism in the precision group and the routine group respectively,and the difference was not statistically significant（P>0.05）;The number of INR<1.2 events in the accurate group was 4（5.1%）and the conventional group was 13（15.3%）,the difference was statistically significant（P<0.05）.Conclusion:（1）Genetic testing can accurately predict the initial anticoagulation dose of warfarin.（2）Genetic testing combined with telemedicine to guide warfarin anticoagulant therapy for NVAF can maintain INR in a more stable range,which is safer than conventional telemedicine group.（3）The TTR of warfarin anticoagulant therapy in patients with NVAF guided by genetic testing combined with telemedicine can reach a higher level at the early stage of anticoagulant therapy,which is more effective than conventional telemedicine group.