急性ST段抬高型心肌梗死患者急诊PCI术中冠脉内注射尿激酶原的有效性与安全性的荟萃分析

Clinical efficacy and safety of intracoronary prourokinase during percutaneous coronary intervention in patients with ST elevation myocardial infarction:a patient pooled meta-analysis of clinical trials

目的系统评价冠状动脉内应用重组人尿激酶原(prourokinase)对急性ST段抬高型心肌梗死患者的有效性与安全性。方法纳入文献9篇,均为RCT试验,共1291人,用药组638人,对照组653人。纳入标准为确诊为急性ST段抬高型心肌梗死的患者。文献检索由2名研究者独立筛选文献,提交资料并交叉核对,如遇分歧则讨论解决,或交由第三名研究者协助判断。统计学分析采用RevMan5.4和Stata17.0进行软件统计Meta分析,二分类变量结局指标采用相对危险度(RR),连续型变量采用加权均数差(WMD)为效应指标,各指标均给出点估值和95%CI。当P>0.05且I^(2)<0.5时采用固定效应模型进行Meta分析。主要观察终点随访期间主要不良心血管事件(MACE)(包括心源性死亡、再发心梗与充血性心衰)。次要观察终点PCI术后冠脉微循环阻塞(包括TIMI3级、cTFC评分、MBG 3级以及心电图ST段回落率>50%);随访期间1月、3月与>6月左心室射血分数;安全终点随访期间出血发生率。结果总计主要不良心血管事件(Major adverse cardiovascular events,MACE)用药组7.1%,对照组11.2%(RR:0.63,95%CI:0.44-0.89,P<0.01,I^(2)=0%)差异有统计学意义,6月以上MACE事件用药组7.6%,对照组12.5%(RR:0.61,95%CI:0.37-0.99,P<0.05,I^(2)=0%)差异有统计学意义。心源性死亡用药组、再发心梗用药组、充血性心衰用药组差异无统计学意义。不同质量文献分析中低质量文献亚组中MACE事件用药组7.1%,对照组14.5%(RR:0.50,95%CI:0.27-0.90,P<0.05,I^(2)=0%),总计文献差异P<0.05,差异有统计学意义。高质量文献差异无统计学意义。次要观察终点,心肌梗死血流3级(Thrombolysis in myocardialinfarction,TIMI,P<0.01)、矫正TIMI计帧数(corrected TIMI frame count,cTFC,P<0.01)、心肌染色分级(myocardial blush grade,MBG,P<0.05)、心电图ST段回落>50%(P<0.01)差异有统计学意义。1月、3月、>6月左心室射血分数,用药组均高于对照组(均P<0.01)。安全终点出血发生率两组无统计学差异。结论PCI术中冠脉内注射尿激酶原可以改善患者冠脉微循环的灌注,从而减少MACE事件,减少心衰发生率,提高患者左心室射血分数。

AIM To evaluate the clinical efficacy and safety of recombinant human urokinase(RH proUK)in patients with acute ST elevation myocardial infarction.METHODS Nine articles were included,all of which were RCT tests,with a total of 1291 people,638 in the drug group and 653 in the control group.The inclusion criteria were patients diagnosed as acute ST segment elevation myocardial infarction.For literature retrieval,two researchers independently screened the literature,submitted the data and cross checked them.In case of disagreement,it was discussed and resolved,or the third researcher assisted in judgment.RevMan5.4 and Stata17.0 were used for software statistical metaanalysis for statistical analysis.Relative risk(RR)was used as the outcome indicator of secondary variables,and weighted mean difference(WMD)was used as the effect indicator for continuous variables.Point estimates and 95%CI were given for each indicator.When P>0.05 and I^(2)<0.5,the fixed effect model was used for meta analysis.Main end point Major adverse cardiovascular events(MACE)during follow-up(including cardiac death,recurrent myocardial infarction and congestive heart failure).Secondary end point:coronary microcirculation obstruction after PCI(including TIMI3,cTFC score,MBG 3 and ECG ST segment fall rate>50%);Left ventricular ejection fraction(LVEF)at 1 month,3 months and>6 months during follow-up;Safety end point:incidence of bleeding during follow-up.RESULTS There was a statistically significant difference in the total major adverse cardiovascular events(MACE)between the drug group(7.1%)and the control group(11.2%)(RR:0.63,95%CI:0.44-0.89,P<0.01,I^(2)=0%).There was a statistically significant difference between the drug group(7.6%)and the control group(12.5%)(RR:0.61,95%CI:0.37-0.99,P<0.05,I^(2)=0%)for MACE events more than 6 months.There was no significant difference among the treatment groups of cardiac death,recurrent myocardial infarction and congestive heart failure.In the sub groups of medium and low quality literature analysis of different quality literature,7.1%of the MACE event medication group and 14.5%of the control group(RR:0.50,95%CI:0.27-0.90,P<0.05,I^(2)=0%),the total literature difference was P<0.05,and the difference was statistically significant.There was no significant difference in high-quality literature.The secondary end points,myocardial infarction blood flow grade 3(TIMI,P<0.01),corrected TIMI frame count(cTFC,P<0.01),myocardial blue grade(MBG,P<0.05),and ECG ST segment regression>50%(P<0.01)were statistically significant.The left ventricular ejection fraction in January,March and>June in the drug group was higher than that in the control group(all P<0.01).There was no statistical difference in the incidence of bleeding at the safe end point between the two groups.CONCLUSION Intracoronary prourokinase during PCI improves microvascular obstruction after PCI,reduces the incidence of MACE and congestive heart failure,and improves LVEF in patients with ST elevation myocardial infarction during follow-up.