| Backgroud and Objective : Amiodarone is a broad-spectrum antiarrhythmic drugs(AADs)which is widely used in clinical.However,its clinical standard program on elderly patients with arrhythmia often causes QT interval(QT)prolongation and increases QT dispersion(QTd)in clinical practice,leading to the risk of torsades de points(Tdp)and other malignant arrhythmias significantly increased,especially for elderly patients who is more than 60 years old.This research is to explore new taking dose and usage regulation of amiodarone for elderly patients with arrhythmia by comparing trend of QT interval,QT interval of heart rate correction(QTc),QT dispersion and QT dispersion of heart rate correction(QTcd)with taking time and total dose,clinical efficacy and adverse reactions of amiodarone after using shortening treatment program and clinical standard protocol for elderly patients with arrhythmia.Therefore,this resarch initially established safety and efficacy of amiodarone for elderly patients in order to guide clinical application of amiodarone for elderly patients.Methods: Randomized controlled trial(RCT)study method is used by this research.A total of 108 elderly patients who diagnosed with ventricular arrhythmias were consecutively collected in Changde NO1.People’s Hospital from October 2016 to October 2017 according to inclusion criteria and exclusion criteria.108 patients were randomly divided into experimental group(group A,n=54)and control group(group B,n=54).Medication method of group A: Shortening treatment program(Newly adjusted dose and usage regimen of amiodarone),that is,oral administration of amiodarone 0.2g each time,every 8 hours,5 days later changed to 0.2g each time,every 12 hours,10 days later changed to 0.2g each time,each day to maintain;Medication method of group B: Clinical standard program(Clinical routine standard usage usage regimen of Amiodarone),that is,oral amiodarone 0.2g each time,every 8 hours,7days later changed to 0.2g each time,every 12 hours,14 days later changed to 0.2g each time,each day to maintain.The complete clinical data of 108 patients,related indicators of the 12-lead body surface electrocardiogram(ECG),24 h Holter monitoring(Holter)which is before taking medicine and one month after discharge,clinical efficacy and adverse drug reactions were recorded.Excel 2003 software,Empower software and R software was used to input,collation and statistical analysis for data.We applied a generalized additive mixture model(GAMM)to draw changes on QT,QT QTc,QTd and QTcd with the taking time and the total dose after using amiodarone in both groups which is after using amiodarone antiarrhythmica,and to adjust for confounding factors affecting QT.The clinical efficacy of two groups after taking the medicine was compared by intention to treat analysis(ITT),per protocol population analysis(PP)and treatment received analysis.The drug safety and compliance of two groups after drug administration were compared.Results:1.Effect of amiodarone on QT,QTc and QTd(1)The incidence of QT>500ms after using amiodarone in the experimental and control groups were 5.56% and 22.22% respectively.There was a statistically significant difference between two groups(P=0.020).(2)In the experimental group,QT,QTc and QTd gradually increased with the prolonged administration time within 7 days after taking medicine.At the 7th day of taking medication,there was a statistically significant difference between posttreatment and pretreatment of QT(P=0.029),and there was no statistically significant difference between posttreatment and pretreatment of QTc and QTd(P=0.885,0.275);Within 7 days to 14 days after taking medicine,QT,QTc and QTd gradually decreased with the prolonged administration time.At the 14 th day of taking medicationn,there was a statistically significant difference between posttreatment and pretreatment of QT(P=0.044),and there was no statistically significant difference between posttreatment and pretreatment of QTc and QTd(P=0.403,0.976);Within 14 days to 30 days after taking medicine,QT gradually increased with the prolonged administration time,QTc and QTd gradually decreased with prolonged medication time.At the 30th day of taking medication,there was a statistically significant difference between posttreatment and pretreatment of QT(P=0.009),and there was no statistically significant difference between posttreatment and pretreatment of QTc and QTd(P=0.262,0.847).(3)In the control group,QT,QTc and QTd gradually increased with the prolonged administration time within 7 days after taking medicine.At the 7th day of taking medication,there was a statistically significant difference between posttreatment and pretreatment of QT(P=0.003),and there was no statistically significant difference between posttreatment and pretreatment of QTc and QTd(P=0.214,0.519);Within 7 days to 14 days after taking medicine,QT,QTc and QTd gradually decreased with the prolonged administration time.At the 14 th day of taking medication,there was a statistically significant difference between posttreatment and pretreatment of QT(P=0.046),and there was no statistically significant difference between posttreatment and pretreatment of QTc and QTd(P=0.823,0.601);Within 14 days to 30 days after taking medicine,QT,QTc and QTd gradually increased with the prolonged administration time.At the 30th day of taking medication,there was a statistically significant difference between posttreatment and pretreatment of QT(P<0.001),and there was no statistically significant difference between posttreatment and pretreatment of QTc and QTd(P=0.086,0.110).(4)At the 7th,14 th,and 30 th days of medication,QT,QTc and QTd were smaller in the experimental group than in the control group.There was no statistically significant difference of QT,QTc and QTd between two groups(P>0.05).There was a statistically significant difference in the trend of QT between two groups with medication time(P=0.033),however,there was no statistically significant difference in the trend of QTc,QTd and QTcd between two groups with medication time(P=0.065,0.535,0.837).2.Clinical efficacy evaluation(1)ITT analysis: The effective rates of amiodarone resistance to ventricular arrhythmia in the experimental group(n=54)and control group(n=54)were 92.59% and 83.33%,respectively,1 month after discharge from hospital.There was no statistically significant difference between two groups(P=0.139).After adjusting for confounding factors by regression analysis,there was no statistically significant difference between two groups(P=0.167).(2)PP analysis: The effective rates of amiodarone resistance to ventricular arrhythmia in the experimental group(n=51)and control group(n=42)were 98.04%and 95.24%,respectively,1 month after discharge from hospital.There was no statistically significant difference between two groups(P=0.864).After adjusting for confounding factors by regression analysis,there was no statistically significant difference between two groups(P=0.650).(3)Treatment received analysis: The effective rates of amiodarone resistance to ventricular arrhythmia in the experimental group(n=56)and control group(n=42)were 98.21% and 95.24%,respectively,1 month after discharge from hospital.There was no statistically significant difference between two groups(P=0.800).After adjusting for confounding factors by regression analysis,there was no statistically significant difference between two groups(P=0.543).The results were consistent by ITT analysis,PP analysis and treatment received analysis,and it indicates that patients who changed groups or did not complete the experimental protocol due to adverse reactions in this study had no effect on the clinical efficacy evaluation of the experimental results,and there is no difference in clinical efficacy between the experimental group and the control group.3.Safety and compliance evaluation(1)Drug safety and compliance:During the experiment,there is no serious malignant arrhythmia or sudden cardiac death between two groups.There was no significant abnormality in blood routine,liver and kidney function,thyroid function,electrolytes,chest radiograph,and lung function at 1 month after discharge.During the follow-up from 6-12 month,no serious adverse reactions occurred and the control of arrhythmia was better.(2)Comparison of adverse reactions: There were 18 adverse reactions during the medication between two groups.The incidence of adverse reactions in the experimental group(7.41%)was lower than the incidence of adverse reactions in the control group(25.93%).There was a statistically significant difference between two groups(P=0.010).After adjusting for confounding factors by regression analysis,there was a statistically significant difference between two groups(P=0.047).The above adverse reactions returned to normal after drug withdrawal.(3)Hemodynamic changes: No hemodynamic disturbances occurred between two groups.Conclusions:1.The shortening treatment program resulted in a lower incidence of QT >500ms than the clinical standard protocol,which improved the safety of amiodarone clinical drug use.2.The shortening treatment program compared to the clinical standard protocol to prolong QT is relatively small,and there was astatistically dsignificant ifference between two programs.The main period for two programs to cause QT prolongation was within 7 days after taking medicine.However,there was no effect on QTc and QTd,and it slows down heart rate slower,and it does not increase repolarization dispersion,therefore the incidence of malignant arrhythmias is low.3.For elderly patients with ventricular arrhythmia who is more than60 years old,there was no statistically significant difference between the shortening treatment program and the clinical standard protocol,but its adverse reactions are less,resulting in a lower incidence of QT interval prolongation and increased safety. |
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