The Efficiency And Safety Of Glycoprotein Ⅱb/Ⅲa Inhibitors For ST Segment Elevation Myocardial Infarction

Objective：1．To perform a meta analysis of the clinical efficiency and safety of early versus lateglycoprotein Ⅱb/Ⅲa inhibitors in ST segment elevation myocardial infarction undergoingpercutaneous coronary intervention, and we also intend to evaluate the efficiency and safetyof early GPⅡb/Ⅲa inhibitors on the basis of adequate clopidogrel.2． To evaluate the efficiency and safety of intracoronary versus intravenousadministration of glycoprotein Ⅱb/Ⅲa inhibitors in patients with ST-segment elevationmyocardial infarction undergoing percutaneous coronary intervention.Methods:We searched for randomized controlled trials in the following databases: PubMed,Embase, The Cochrane library, CBM and CJFD. Besides, according to the CochraneHandbook, we searched relative websites for unpublishment and grey literatures, andobtained the latest trials through the Google search and manual search. We read the abstract,and screen literature through give attention to patient, intervention, control, outcomes. Trialquality was scored using a quality assessment form based on Cochrane systematic reviewguidelines. This scale assessed sequence generation, allocation sequence concealment,blinding, incomplete outcome data, selective outcome reporting, and other potential sourcesof bias. Data extraction was conducted by two reviewers independently. Disagreementswere resolved through discussion or contact author through email. All data were analyzedby using Review Manager5.1. Currently, three intravenous GpⅡb/Ⅲa inhibitors areavailable: the monoclonal abciximab and the small-molecule glycoprotein Ⅱb/Ⅲa inhibitors(SMGP), namely eptifibatide and tirofiban. Significant differences exist between theclinical outcome of abciximab and SMGP following PCI procedures. Therefore, themeta-analysis of pre-specified subgroups was performed according to abciximab and SMGPadministration. Results:1. The first part is mainly to evaluate the efficiency and safety of early versus lateadministration of GP Ⅱb/Ⅲa inhibitors in STEMI undergoing PCI. Nineteen randomizedtrials were included in the final meta-analysis, and a total of4209patients were included,2124patients (50.5%) were randomly assigned to early GpⅡb/Ⅲa inhibitor administrationand2085patients (49.5%) were subjected to late administration. Meta analysis showed that:Compared with late administration of abciximab, early admistration can significantimproved the incidence rates of Pre-procedure thrombolysis in myocardial infarction (TIMI)flow grade3(RR=2.14，95%CI1.46to3.14，P <0.01), Post-procedure TIMI flow grade3(RR=1.05,95%CI1.00~1.09，P=0.04), complete ST-segment resolution (RR=1.31，95%CI1.12~1.53，P <0.01), left ventricular ejection fraction (MD=0.04，95%CI0.01~0.07，P<0.01), reduced six-month mortality (RR=0.36，95%CI0.14~0.92，P=0.03), and withoutincrease the incidence of TIMI defined major bleeding (RR=1.50，95%CI0.96~2.36，P=0.08). However, there were no difference in3-month mortality between the early and lategroup (RR=1.00，95%CI0.69~1.43，P=0.98). In addition to clopidogrel, early abcixiabcan only inproved pre-procedural TIMI3flow (RR=2.58，95%CI1.47~4.55，P <0.01) andcomplete ST-segment resolution (RR=1.30,95%CI1.01~1.68, P=0.04), but alsowithout increase the TIMI defined major bleeding (RR=1.53,95%CI0.58~4.01, P=0.39).Early versus late administration of SMGP can only significantly improved pre-procedureTIMI flow grade3(RR=1.70,95%CI1.21~2.37, P<0.01), there were no difference inpost-procedure TIMI flow grade3(RR=1.00，95%CI0.97~1.04，P=0.81), completeST-segment resolution (RR=1.02，95%CI0.85~1.22，P=0.84), left ventricular ejectionfraction (MD=0.02，95%CI-0.00~0.04, P=0.10),3-month mortality (RR=1.57,95%CI0.89~2.77, P=0.12), and TIMI defined major bleeding (RR=1.21,95%CI0.52~2.81, P=0.66).2． The second part is mainly to evaluate the intracoronary versus intravenousadministration of glycoprotein Ⅱb/Ⅲa inhibitors in primary percutaneous coronaryintervention of ST-segment elevation myocardial infarction. Eleven randomized trials wereincluded in the final meta-analysis, and a total of1569patients were included,799patientswere randomly assigned to intracoronary GpⅡb/Ⅲa inhibitor administration and770patients were subjected to intravenous administration. Meta analysis showed that: Compared with intravenous administration of GP Ⅱb/Ⅲa inhibitors, intracoronary route cansignificant improved the incidence rates of Post-procedure thrombolysis in myocardialinfarction (TIMI) flow grade3(RR=1.08,95%CI1.04~1.13, P<0.01), Post-procedure TIMImyocardial perfusion grade (TMPG)3(RR=1.37,95%CI1.16~1.63, P<0.01), one-monthmajor adverse cardiac events (RR=0.48,95%CI0.34~0.69, P<0.01) and the recovery of leftventricular ejection fraction (MD=0.04,95%CI0.02~0.06, P<0.01), without increase theincidence of TIMI defined major bleeding (RR=1.04,95%CI0.55~1.95, P=0.90). Besides,abciximab was associated with a significant reduction in one-month mortality (RR=0.45,95%CI0.21~0.99, P=0.05).Conclusion:1. Early versus late administration of GP Ⅱb/Ⅲa inhibitors can significantly inprovedpre-procedure TIMI flow grade3and without increase the TIMI defined major bleeding inthe STEMI undergoing PCI. On the basis of those, early abciximab can further improvedmyocardial perfusion, left ventricular function, and clinical prognosis. On the basis ofadquete clopidogrel, early abciximab still can improved pre-procedure TIMI flow grade3and complete ST–segment resolution, also without increase the incidence of majorbleeding. So on the existente evidence, early abciximab is recommend to the STEMI undergoing PCI.2．Compared with intravenous administration of GP Ⅱb/Ⅲa inhibitors, intracoronaryroute can improved the Post-procedure TIMI flow grade3, Post-procedure myocardialreperfusion, one-month major adverse cardiac events and recovery of left ventricularejection fraction, without increase the incidence of bleeding. On the basis of those,abciximab can further improve the incidence of one-month death..