Individualized Efficacy Evaluation Of Hypertensive Drugs In The Real-world Community Population

Background:Hypertension is a major disease that threatens the population health.It is an important culprit in high burden diseases such as cardiovascular,cerebrovascular diseases and chronic kidney disease in the national population.The Chinese people’s DALYs due to high blood pressure was as high as 10 million person-years,accounting for about one-tenth of the total DALYs and half of the total DALYs of cardiovascular disease.At present,the awareness rate,treatment rate and control rate of hypertension in China are far from the level of developed countries.The treatments of hypertension are mainly non-medication treatment and medication treatment.Medication treatment is the most important measure to control high blood pressure and antihypertensive drugs include diuretics,beta-blockers,angiotensin-converting enzyme inhibitors and angiotensin receptor’blockers.Although the efficacy and safety of these drugs have been validated by standard clinical trials and have been promoted in the guidelines for the prevention and treatment of hypertension,a large number of studies have found that the population has a low rate of hypertension control,especially in rural population.At present,most studies on the awareness,treatment and control of hypertension are cross-sectional surveys,and there are few long-term observations and follow-up studies.However,it is difficult to evaluate the effects of drug interventions objectively,especially for individualized interventions in real-world populations,where randomized distribution is difficult and the effects of both medication and non-medication treatments tend to mix.Therefore,there is no scientific basis for the development of hypertension control measures and policies in the community.Therefore,it is of great practical significance to evaluate objectively the effects of antihypertensive drug interventions(especially individual treatment effects)and to formulate antihypertensive drugs intervention policies and to select essential hypertensive drugs in the real-world communities relying on long-term hypertension management follow-up cohort.Objectives:To evaluate the therapeutic effects of commonly used antihypertensive drugs,and to provide decision-making basis for essential antihypertensive drug screening and individualized intervention measures in real-world communities.Methods:To design a real-world study of community interventions for hypertension,and to build a community population hypertension drug treatment intervention follow-up cohort based on Qingdao Jiaonan basic public health services for chronic disease management projects.Furthermore,the average efficacy and individualized efficacy were evaluated for specific drug prescriptions based on the observation and follow-up results in the real-world prevention and treatment practice.① Relying on the"Jiaonan Health Bureau Hypertension Comprehensive Prevention and Control Project",a follow-up management cohort of hypertensive drug intervention was established by adopting the strategies of screening,listing and treatment intervention at the same time.The duration of the cohort observation was between January 1,2011 and December 31,2015.During the follow-up management intervention period,a total of 61123 hypertension patients over 35 years old were observed.②The baseline characteristics of the cohort were analyzed to obtain the prescription profiles of hypertension drugs in the real-world community population by conventional cohovrt analysis and inferred the association between medication and outcome(hypertension control rate),and evaluated the intervention compliance and its influencing factors.③ On the basis of cohort analysis,the propensity score matching method was used to design the quasi-randomized trial,so that the important confounders affecting the efficacy of drug could reach the groups equilibrium and comparison.④ To evaluate the average treatment effect of antihypertensive drugs(captopril,nitrendipine,compound reserpine,combined captopril and nitrendipine)under the strong ignorability based on the quasi-randomized trial.⑤The individualized causal learning algorithm-uplift modelling was applied to predict the counterfactual potential outcome effect of individuals,estimated the individualized intervention effect of drug prescription and identified the individualized intervention characteristics by modified outcome method,causal conditional inference forests and uplift random forests model.Results:1.The prescriptions of hypertension in real-world community were of obvious diversity.Hypertension patients with single drug accounted for 72.42%,double drugs combination accounted for 23.37%and triple drugs combination accounted for 4.21%.There were 18 prescriptions for single drugs,and half chose captopril.There were 59 prescriptions for the combination,with captopril and aspirin being the most popular.A total of 15 prescriptions were included in the three-drug combination,with the largest number of prescriptions being the combination of captopril,nitrendipine and aspirin.Single drug still accounted for the majority of the hypertension population,and unreasonable drug use still existed in the real-world.2.The intervention effect on smoking,drinking,obesity,exercise and other lifestyle was difficult to maintain for a long time,had a little effect on the long-term intervention,but the intervention effect gradually disappeared,or even rebounded with the extension of follow-up time.3.The main factors affecting the blood pressure control of patients with hypertension were medication compliance and whether they reached the standardized management level.The specific performance was as follows:① with the process of follow-up intervention,the blood pressure control rate of the regular medication group,intermittent medication group and non-medication group all showed a gradually increasing trend,the average control rate reached 50%.Among them,the control rate of hypertensive patients taking medicine regularly was the highest,followed by the intermittent medication group,and finally the non-medication group.②Standardized management group and non-standardized management group of hypertension control rate showed an increasing trend.However,the blood pressure control rate of the standardized management group was much higher than that of the non-standardized management group.③ Age and gender of patients had little influence on the compliance rate of hypertension control.4.The standardized management of hypertension patients was the most critical factor affecting their medication compliance.The results showed that the non-medication rate of hypertension patients in the non-standardized management group decreased gradually,the regular medication rate increased gradually,and the intermittent medication increased first and then decreased.The non-medication rate of hypertension patients in the standardized management group decreased slowly,the regular medication rate increased gradually,and the intermittent medication first decreased,then increased and then decreased.The overall rate of non-medication was higher in the non-standardized management group than in the standardized management group,and the regular medication rate was higher in the standardized management group than in the non-standardized management group.5.Using the propensity score matching obtained quasi-randomized design,this study found that in the community population,the control rates of captopril,nitrendipine,compound reserpine,and combined captopril and nitrendipine were all above 20%,and the control rates of them were statistically dif-ferent from those of the non-taking group.However,the average treatment effect(control rate decreased%)was not as good as that of the non-drug group,whose captopril was 4.01(2.73,5.28),nitrendipine was 7.01(4.73,9.29),compound reserpine was 9.05(4.86,13.23),and combined captopril and nitrendipine was 11.28(8.24,14.32).However,through the individualized efficacy evaluation of uplift random forests model,it was found that all kinds of drugs had their specific suitable individuals,for which the blood pressure control effect was obvious.Specifically,①the blood pressure control effect of captopril was better in 37.95%of patients.These individuals were characterized by being older,overweight,having light hypertension,low labor intensity,not smoking,not drinking,and exercising.②69.94%of the patients taking nitrendipine was good.These individuals were characterized by being younger,overweight,having light hypertension,heavy labor intensity,not smoking,not drinking,and exercising.③78.07%of the patients taking compound reserpine was good.These individuals were characterized by being older,not fat,having light hypertension,moderate labor intensity,not smoking,not drinking,and not exercising.④ 97.80%combined captopril and nitrendipine was better.These individuals were characterized by being older,overweight,having severe hypertension,moderate labor intensity,not smoking,not drinking,and not exercising.Conclusions:1.Single drug still accounted for the majority of hypertensive patients in real-world community,and the phenomenon of unreasonable drug still existed.Therefore,the guideline of hypertensive drugs should be further improved.And community doctors should also be trained.2.It was difficult to maintain the effect of lifestyle intervention for a long period of time,and intervention usually had a little effect for a long period of time.However,the effect of intervention gradually disappeared or even rebounded.3.The main factors affecting the blood pressure control were the adherence to medication and whether they reached the standardized management level.4.The standardized management of hypertensive patients was the most critical affecting their adherence to medication.5.Through the average blood pressure control rates of captopril,nitrendipine,compound reserpine and combined captopril and nitrendipine were unsatisfactory in real-world community hypertension population,individual treatment efficacy evaluation found that four kinds of prescriptions were suitable for specific subgroups whose effect had better blood pressure control effect by uplift random forest model.