The Best Intervention Time Of Activating Blood Circulation To Remove Stasis And Dredging In The Perioperative Of Myocardial Infarction

ObjectivesThe current clinical studies of Danhong injection(DHI)intervention for myocardial infarction(MI)with percutaneous coronary intervention(PCI)have been inconsistent in the selection and reporting of outcome indicators,and none of them focused on the differences in efficacy between different time.1 Constructed a core outcome set for MI perioperative with the intervention of Chinese herbal injection,standardize the selection of outcome indicators in clinical studies,and promote the transformation of study results to high-level evidence.2 Based on the known good efficacy and high safety of DHI in the perioperative period of MI,optimizing the specific timing of DHI in the perioperative period,providing scientific evidence for the formulation of relevant guidelines.Methods1 To address the inconsistencies and irregularities in the selection and reporting of outcomes in current studies,we used systematic review to sort out all outcome indicators reported in randomized controlled trials(RCTs)of PCI intervention with Chinese herbal injections,form an initial list of outcomes,and count the cumulative reporting frequency.On the basis of the initial list of outcomess,we conducted a Delphi survey to select a list of important indicators based on the ratings of outcomes by relevant interest groups.The outcomes reported in the top 30% of the systematic review and with a score of ≥7 in the Delphi survey were combined to build a core outcomes set for perioperative with Chinese herbal injection.2 Based on the core outcome set,we selected a representative drug for activating blood circulation,resolving blood stasis and promoting blood circulation—DHI to carry out a Meta-analysis.To evaluate the overall efficacy of DHI,relative risk(RR)was used for dichotomous variables,and mean difference(MD)was used for continuous variables.95% Confidence interval(95% CI)and P value were used to determine whether the difference was statistically significant.Subgroup analysis was used to compare the differences in the efficacy of DHI at different timing in the perioperative period.3 A clinical retrospective cohort study based on real-world data was conducted.We collected medical records of patients diagnosed with MI and undergoing PCI from January 1,2019 to December 31,2021 at Jiangxi Provincial People’s Hospital and the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine.The use of DHI as the exposure factor,the patients were divided into exposed and non-exposed groups,and compared the efficacy and safety of the two groups.The exposed groups were further grouped to analyze the differences in efficacy and safety at different times,validating the results of the Meta-analysis in the previous section.Results1 Construction of core outcome setOn systematic review,55 outcomes reported in 114 RCTs of perioperative PCI with Chinese herbal injections constituted the original list of outcomes.55 outcomes were reported 576 times in cumulative frequency,and the top 30% were: LVEF,MACEs,CK-MB,TIMI flow classification,adverse effects,hs-CRP,LVED,SOD,LVSD,IL-6,ST-segment regression,c Tn T,BNP,MDA,clinical efficacy,c Tn I,NO,NT-pro BNP,TNF-ɑ,CK,CRP,ET,and cardiac function.By Delphi survey,56 MI-related interest groups screened outcomes those they considered important,and outcomes with scores ≥7 were: incidence of MACEs,clinical efficacy score,CK-MB,c Tn I,all-cause mortality,recurrent flow,ST-segment regression,TCM evidence score,c Tn T,LVEF,QRS score,hs-CRP,PT,Fib,D-dimer,LVDF,heart rate,IL-6,CK,TIMI flow classification,myocardial infarct size,IL-7,LVSF,cardiac function,ET,CRP,IL-8,and adverse events.The final core outcome set was constructed,containing a total of 10 outcomes:MACEs,LVEF,TIMI flow grading,ST-segment regression,CK-MB,c Tn T,c Tn I,hsCRP,IL-6,and adverse effects.2 Clarified the efficacy of DHI at different times in the perioperative of PCI based on a Meta-analysisMeta-analysis of 26 RCTs of DHI in the perioperative of PCI,including 3preoperative(n = 460),4 intraoperative(n = 359),1 intraoperative continuous postoperative(n = 166),and 18 postoperative(n = 2049).Overall,the combination of DHI and conventional treatment reduced the incidence of MACEs(RR = 0.50,95% CI[0.42 to 0.61]),c Tn T(MD =-0.76,95% CI [-1.04 ～-0.48]),CK-MB(MD =-1.51,95%CI [-2.41 ～-0.60]),hs-CRP(MD =-0.85,95% CI [-1.09 ～-0.61])and IL-6(MD =-1.10,95% CI [-1.48 ～ 0.71])levels,improving LVEF(MD = 1.30,95% CI [0.96 ～1.65])and promoting reperfusion(RR = 1.14,95% CI [1.07 ～ 1.20 ]).Subgroup analysis of different timing in the perioperative showed that for TIMI blood flow,DHI was superior to the control group for preoperative(RR = 1.12)and intraoperative(RR = 1.22)interventions(P < 0.05),with no statistically significant difference between the two groups for postoperative(P = 0.654).Intraoperative administration of DHI and continued at a dose of 4 m L/day for 14 days postoperatively improved LVEF better than other time points(MD= 2.34,P < 0.001).Preoperative(MD=-0.77)and postoperative(MD=-0.83)DHI interventions were able to significantly reduce hs-CRP levels(P < 0.05),but the difference between the intraoperative intervention DHI group and the control group was not statistically significant(P=0.180).The postoperative study was analyzed in subgroups according to the different courses and doses.The results showed that different doses lowered IL-6,30 m L/day was more effective than 20 m L and 40 m L(P < 0.001).CK-MB reduction by different courses of treatment was better for 10 days than for 7 and 14 days(P < 0.001).Hs-CRP reduction was better for 14 days of application than for 7 and 10 days(P = 0.010).3 Validied of the overall efficacy of DHI and different efficacy of perioperative time points based on real-world studyA total of 289 cases(165 in the exposed group and 124 in the non-exposed group)were included for retrospective analysis,and baseline information such as gender,age,medical history,personal history,heart rate,blood pressure,and predisposing factors were not different between the two groups and were comparable.After treatment,the incidence of MACEs was significantly lower in the exposed group than in the nonexposed group(RR=0.38,P=0.022),the reduction in the no-reflow rate was better than in the non-exposed group(P=0.023),and the improvement in CK-MB,c Tn I,D-dimer,glutamic aminotransferase,creatinine,and urea nitrogen was better than in the control group(P<0.05).In the exposed group,there were 26 cases of preoperative,5 cases of intraoperative,69 cases of postoperative,and 65 cases of total intervention.There were no statistical differences between the groups in terms of demographic characteristics,co-morbidities,predisposing factors and number of diseased vessels at baseline.In terms of efficacy outcomes,CK-MB and c Tn I were significantly higher in the intraoperative group than in other groups before DHI intervention(P < 0.05),and there were no differences between groups after intervention.There were no differences in other indexes between groups(P > 0.05).As for the safety outcomes,the blood routine,liver function and kidney function indexes fluctuated within the normal range in all groups.Conclusion1 The core outcomes in the perioperative of PCI are: incidence of MACEs,LVEF,TIMI flow classification,ST-segment regression,CK-MB,c Tn T,c Tn I,hs-CRP,IL-6,and adverse events.2 DHI is effective in the perioperative period of PCI,reducing the incidence of MACEs,promoting reperfusion,restoring cardiac function,and reducing levels of inflammatory factors and myocardial injury,without increasing safety events.It is particularly effective in improving TIMI flow classification preoperatively and intraoperatively,reducing hs-CRP levels with preoperative and postoperative application,and enhancing LVEF with intraoperative persistence into the postoperative period,intraoperative application of Danhong injection is most effective in reducing CK-MB and c Tn I.30 m L/d is recommended for patients with high IL-6 levels,a 10-day intervention course is recommended for patients with significant CK-MB abnormalities,and 14 days is recommended for patients with high hs-CRP.The current real-world studies cannot fully confirm the RCTs’ Meta analysis results,further welldesigned,multicenter studies with large samples are needed.