| Purpose: To evaluate the efficacy and safety of removing blood stasis and expelling phlegm,invigorating spleen and detoxifying in the treatment of non-ST-segment elevation acute coronary syndrome(NSTE-ACS),to explore the expression of inflammatory factors(groups)in patients with recurrent cardiac events of NSTE-ACS,and to explore the relationship between inflammatory factors(groups)and recurrent cardiac events of NSTE-ACS.Material and method: 1.The first part In this study,a multi-center,prospective cohort clinical trial design was adopted.The patients with NSTE-ACS were taken as the study population,and Chinese herbal granules for removing blood stasis and detoxification were used as exposure factors.According to whether to use Chinese herbal granules for removing blood stasis and expectoration and invigorating spleen and detoxifying,two cohorts were divided into two groups: a cohort of integrated Chinese and Western medicine and a cohort of Western medicine,140 cases in each group.Both groups were given routine western medicine treatment,and Chinese medicine granules of "removing blood stasis and expelling phlegm,invigorating spleen and detoxifying" were added to the cohort of integrated medicine.The course of treatment was 24 weeks,followed up until February 4,2019.Endpoint outcomes(ischemic chest pain re-admission,ST-segment elevation acute myocardial infarction,revascularization,all-cause death)were recorded.The incidence of endpoint outcomes,incidence density,survival analysis,levels of inflammatory factors(high-sensitivity C-reactive protein,interleukin-6,interleukin-10,matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1),angina integral changes and Seattle Angina Scale changes were analyzed to evaluate the clinical efficacy and safety of "removing blood stasis and expelling phlegm,invigorating spleen and detoxifying" in the treatment of NSTE-ACS.2.The second part A nested case-control clinical trial design was adopted.The cohort of integrated traditional Chinese and Western medicine of the first part was ranked as the baseline cohort.Patients with recurrent cardiovascular events during follow-up period were selected as the case group.Tendency score was used to match the control group in a ratio of 1:2 in terms of age,sex,height and weight.The expression of 40 inflammatory factors in serum of the two groups was detected by protein chip,and the relationship between inflammatory factors and recurrent cardiovascular events of NSTE-ACS was analyzed.Results: 1.The research results of the first part 1.1 Inclusion,loss of follow-up and completion of the study All the patients were NSTE-ACS,which met the criteria of rejection.Two hundred and seventy-seven cases were included according to the admission plan.One hundred and thirty-eight cases were included in the cohort of integrated traditional Chinese and Western medicine,and 139 cases were included in the cohort of Western medicine.A total of 8 people were lost.One hundred and thirty-eight cases were completed in the cohort of integrated Chinese and Western medicine,135 cases were completed in the cohort of Western medicine.The rate of lost visits was 2.90% and 2.87% respectively.The compliance rate of subjects in the cohort of integrated Chinese and Western medicine was 96.83%.1.2 Endpoint outcome comparison 1.2 Comparison of end point outcomes Up to the follow-up deadline,there were 16 recurrent cardiovascular events in the cohort of integrated Chinese and Western medicine,and 28 recurrent cardiovascular events in the cohort of Western medicine.There was no significant difference in the number of recurrent cardiovascular events between the two cohorts(P=0.051).In terms of density,this study adopt person-months as the unit.The result shows that the incidence density of the integrated Chinese and Western medicine cohort was 7.13 ‰ person-months,while the incidence density of the Western medicine cohort was as high as 17.25 ‰ person-months,which was 2.42 times that of the integrated Chinese and Western medicine cohort.χ2=8.381,P=0.004<0.05,which indicates that on the onset of density,combine traditional Chinese and western medicine queue was significantly lower than western medicine,the difference was statistically significant.The survival time of patients with recurrent cardiovascular events was analyzed as the prescribed outcome.There was significant difference between the two groups(P<0.01).The survival curve of the cohort of integrated Chinese and Western medicine was above the cohort of Western medicine.It shows that the cohort of integrated traditional Chinese and Western medicine is superior to the cohort of Western medicine in delaying the recurrence of cardiovascular events.Cox model analysis showed that angina score,hs-CRP and interventions were independent prognostic factors for recurrent cardiovascular events in NSTE-ACS.The regression coefficient of intervention measures was less than 0,indicating that the integrated Chinese and Western medicine cohort was a protective factor for the recurrence of cardiovascular events in NSTE-ACS,and the relative risk(RR)was 0.388,indicating that the risk rate of recurrence of cardiovascular events in the integrated Chinese and Western medicine cohort was 38.8% of that in the Western medicine cohort,suggesting that the combined Chinese and Western medicine therapy could reduce the incidence of recurrence of cardiovascular events in NSTE-ACS.The regression coefficients of pain score and C-reactive protein were both greater than 0,suggesting that both were adverse factors for recurrence of cardiovascular events in NSTE-ACS.With the increase of angina score and C-reactive protein concentration,the risk of recurrence of cardiovascular events in NSTE-ACS also increased.1.3 Comparison of inflammatory factors After 24 weeks of intervention,the results showed that there were significant differences in hs-CRP,IL-6,IL-10,MMP-9 and TIMP-1 between the two groups(P<0.05),and the mean values of hs-CRP,IL-6 and MMP-9 were significantly lower than those before treatment,while the values of IL-10 and TIMP-1 were significantly higher than those before treatment(P<0.05).The baselines were comparable except IL-10.After 24 weeks of intervention,the decrease of hs-CRP,IL-6 and MMP-9 in the cohort of integrated traditional Chinese and Western medicine was better than that in the cohort of Western medicine(P< 0.05).In the improvement of TIMP-1,there was no difference between the two cohorts after 24 weeks of intervention(P>0.05).The baseline of IL-10 was uneven between the two groups,and the difference of IL-10 between the two groups was significant after 24 weeks of intervention(P<0.05).1.4 Comparison of Angina Pectoris Integral Scales The baseline score of 0 weeks was comparable between the two groups.Except for the duration of angina,the other four scores were different between the two groups at 12 weeks and 24 weeks(P<0.05).The results of anovariance analysis of single-group repeated measures showed that both groups declined with the prolongation of time(P<0.05)in terms of total score of angina pectoris,the number of attacks of angina pectoris and the duration of angina pectoris.As for the pain score of angina pectoris,the cohort of integrated traditional Chinese and Western medicine decreased with the prolongation of time(P<0.05),and the cohort of Western Medicine showed a downward trend as a whole(P<0.05),but there was no difference between 0 and 12 weeks(P>0.05).On the score of nitroglycerin dosage,the cohort of integrated traditional Chinese and Western medicine decreased with the prolongation of time(P<0.05),and the cohort of Western Medicine showed a downward trend as a whole(P< 0.05),but there was no difference between 12 weeks and 24 weeks(P>0.05).The results of variance analysis of repeated measurements showed that P of time effect(time)of the two queues was less than 0.05 in five aspects of the angina score table,indicating that the five aspects of the two queues showed a downward trend,and the difference was statistically significant.In addition to the duration of angina pectoris score,the P of time interaction effect(group * time)in the other four aspects were less than 0.05,indicating that there was interaction between measurement time and cohort.The variance analysis of the inter-group effect(group)showed that except for the pain score of angina pectoris,the decreasing trend of the cohort of integrated traditional Chinese and Western medicine was better than that of the cohort of Western medicine,and the difference was statistically significant(P<0.05).1.5 Seattle Angina Scale The Seattle Angina Scale is divided into five items: physical activity limitation(PL),stable state of angina(AS),angina attack(AF),treatment satisfaction(TS)and disease awareness(DS).The baseline score of 0 weeks was comparable between the two groups in the five items of the Seattle Angina Scale.At 12 weeks of intervention,except for PL,there were no differences in the other four aspects between the two groups(P>0.05).At 24 weeks of intervention,except TS and DS,there were significant differences between the two groups(P<0.05).The results of anovariance analysis of single-group repeated measures showed that both groups rised with the prolongation of time(P<0.05)in terms of AS,AF and DS.As for the PL,the cohort of integrated traditional Chinese and Western medicine rised with the prolongation of time(P<0.05),and the cohort of Western Medicine showed a rising trend as a whole(P<0.05),but there was no difference between 0 and 12 weeks(P>0.05).On the TS,the cohort of integrated traditional Chinese and Western medicine showed a rising trend as a whole(P<0.05),,but there was no difference between 12 weeks and 24 weeks(P>0.05)and the cohort of Western Medicine rised with the prolongation of time(P<0.05).The results of variance analysis of repeated measurements showed that P of time effect(time)of the two queues was less than 0.05 in the five items of the Seattle Angina Scale,indicating that the five aspects of the two queues showed a rising trend,and the difference was statistically significant.In addition to the TS and DS,the P of time interaction effect(group * time)in the other three aspects were less than 0.05,indicating that there was interaction between measurement time and cohort.The variance analysis of the inter-group effect(group)showed that except for AF,TS,and DS,the rising trend of the cohort of integrated traditional Chinese and Western medicine was better than that of the cohort of Western medicine,and the difference was statistically significant(P<0.05).1.6 Safety Indicators In terms of safety evaluation,there were no abnormalities in blood routine,urine routine,stool routine,liver function,kidney function and blood coagulation after 24 weeks of intervention compared with 0 weeks.No serious adverse events occurred during the study.There were 8 cases of mild adverse reactions in the cohort of integrated Chinese and Western medicine,and 6 cases in the cohort of Western medicine.Chi-square test showed that χ2= 0.317,P=0.573,there was no significant difference.2.The research results of the second part2.1 General information and baseline information As of February 4,2019,16 patients in the cohort of integrated Chinese and Western medicine had cardiovascular events as the case group,one of them was ST-segment elevation myocardial infarction(ST-segment elevation myocardial infarction).Thirty-two cases of control group were matched by propensity score according to 1:2.Except for total cholesterol(P=0.027),triglyceride(P=0.018),and short-term risk stratification(P=0.024),the differences between the two groups were not statistically significant(P>0.05).2.2 Expression and distribution of inflammatory factors in two groups The intensity of fluorescence signal in inflammatory factor chip was transformed to form the signal value of each inflammatory factor in each serum.By comparing the protein signal value of serum factor in 40 patients of the two groups,it was found that there were significant differences in three inflammatory factors between the two groups(P<0.05).The three inflammatory factors were MIP-1alpha,IL-12 p70 and I-309,and the expression of the three inflammatory factors in the case group was down-regulated compared with the control group.2.3 Conditional logistic regression analysis of cardiovascular events affecting the recurrence of NSTE-ACS The factors influencing the recurrence of cardiovascular events in NSTE-ACS were explored by taking the recurrence of cardiovascular events in NSTE-ACS as dependent variable.Because there are many influencing factors involved,there are only 48 samples in this nested case-control study.According to the relationship between independent variables and sample size in conditional logistic regression analysis,this analysis only takes the three inflammatory factors(MIP-1alpha,IL-12 p70 and I-309)levels which are different between the two groups as independent variables,and substitutes them for conditional logistic regression equation.The results did not lead to factors associated with the recurrence of NSTE-ACS.Conclusion: 1.Removing blood stasis and expectorating phlegm,invigorating spleen and detoxifying can reduce the recurrence rate of cardiovascular events in NSTE-ACS patients,improve the level of inflammatory factors in patients’ serum,improve the clinical symptoms and quality of life of patients with fewer adverse reactions.2.MIP-1alpha,IL-12 p70 and I-309 may be involved in the process of recurrence of cardiovascular events in NSTE-ACS,and further large-scale clinical studies are needed to confirm this.. |
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