| Objective:To prospectively study the variations of platelet inhibition rate（ADP inhibition rate）in ACS patients with CYP2C19 intermediate metabolism（CYP2C19*1/*2,CYP2C19*1/*3）after percutaneous coronary intervention（PCI）,patients were treated with double-dose clopidogrel or routine dose ticagrelor at different time points including before PCI（before taking the medicine）,on the 30th day and 90th day after PCI.The incidence of major adverse cardiovascular events（MACE events）,bleeding events and dyspnea events were also evaluated on the 1st month,3rd month and 12th month after PCI in order to compare the efficacy and safety of the two treatments.The concentrations of hs-CRP,IL-2 and IFN-γwere also detected to compare the anti-inflammatory effects of clopidogrel and ticagrelor at different time points including before PCI（before taking the medicine）,on the 1st day,7th day,30th day and 90th day after PCI.Methods:325 ACS patients with CYP2C19 intermediate metabolizers（CYP2C19*1/*2,CYP2C19*1/*3）hospitalized into the department of cardiology of the affiliated hospital of Qingdao university and received PCI were selectedfrom January to October 2016.All 325patients were randomly divided into clopidogrel group（158 cases）and ticagrelor group（167cases）.Both groups received routine dose of aspirin（100mg,qn）.The patients in the clopidogrel group were administered with double dose clopidogrel（150mg,qd）while those in the ticagrelor group were given routine doseticagrelor（90mg,bid）.The two groups of patients were required to apply oral antiplatelet therapy for at least 12 months.while other drugs such as nitrates,statins,ACEI,Beta blockers and CCB were used according to individual conditions.Coronary angiography and percutaneous coronary intervention were performed via radial or femoral artery among all the selected patients.Coronary angiography and interventional therapy were used to observe the coronary artery lesions and to judge the degree of coronary artery stenosis and the effects of stent implantation.All operations were performed by the same interventional operation team.The CYP2C19 gene polymorphism was detected by gene chip and the ADP inhibition rate was detected using thrombelastography before PCI（before taking the medicine）.The ADP inhibition rate was also detected on the 30th day and 90th day after PCI.Peripheral venous blood samples of the patients were extracted and concentrations ofhs-CRP,IL-2 and IFN-γwere detected respectively before PCI（before taking the medicine）,on the 1st day,7th day,30th day and90th day after PCI.All patients were followed-up on the 1st month,3rd month and 12th month after PCI to record their MACEs,bleeding events and dyspnea events.Datas were analyzed by SPSS22.0.All categorical variables were described with percentage（%）and were tested by?2 test or Fisher exact test.All measurement data was expressed as mean±standard deviation(<sub></sup>x±s).Comparison of quantitative indicators at different time points in the group was analyzed by repeated measures analysis of variance,and the quantitative indicators between the two groups were analyzed by independent sample t test,the Comparison of two-two inmultiple groups were analyzed by SNK test.P<0.05 indicated a statistical significance.Results:1.Compared with clinical baseline data between the two groups:There were no statistical differences in age,sex,smoking history,family history,hypertension history,diabetes history,blood lipids,renal function,liver function,troponin,white blood cell count,platelet count between the two groups.（P>0.05）.2.Compared with PCI results between the two groups:There were no significant differences between the two groups in lesion site,operation complexity,length and diameter of the stents,pressure of balloon dilatation,pressure of stent release,ratio of post-balloon dilatation,postoperative TIMI blood flow and operation time（P>0.05）.3.Compared with ADP inhibition rates between the two groups before PCI（before taking the medicine）,on the 30th day and 90th day after PCI:There were no significantly differences of the ADP inhibition rate between the two groups before PCI（before taking the medicine）（P>0.05）.The ADP inhibition rate of the two groups on the 30th day after PCI was higher than that before PCI（P<0.05）,especially in the ticagrelor group（P<0.05）.There was no significant difference in both groups on the 90th day after PCI than that on the 30th day（P>0.05）.However,the increase in the ticagrelor group was more obvious,there was significant difference between the two groups（P<0.05）.4.Compared with MACEs between the two groups after PCI on the 1st month,3rd month and 12th month:4 cases of MACEs occurred on the 1st month after PCIin clopidogrel group,including 3 cases of unstable anginapectoris and 1 case of acute myocardial infarction.1 case of unstable angina pectoris occurred on the 1st month after PCI in ticagrelor group.There was a significant difference between the two groups（P<0.05）.4 new casesof MACEs occurred during the follow-up period of the 3rd month in clopidogrel group which include 2 cases of unstable anginapectoris,1 case of acute myocardial infarction and 1 case of sudden cardiac death.3 new cases of MACEs during the follow-up period of the 3rd month in ticagrelor group which include 2 cases of unstable angina pectoris and 1 case of acute myocardial infarction.There was no significant difference between the two groups in new cases（P>0.05）.While there was a significant difference between the two groups in the overall cases（P<0.05）.11 cases of MACEs occurred on the 12th month after PCI in clopidogrel group,there were 3 new cases which include 2 unstable angina pectoris and 1acute myocardial infarction.5 cases of MACEs on the 12th month after PCI in ticagrelor group,there was 1 new case of unstable angina pectoris.There was no significant difference between the two groups in new cases（P>0.05）.While there was a significant difference between the two groups in the overall cases（P<0.05）.5.Compared with bleeding events of patients between the two groups after PCI on the1st month,3rd month and 12th month:1 case of bleeding event occurred in clopidogrel group on the 1st month.3 cases of bleeding events occurred in ticagrelor group on the 1st month,which were all mild bleeding events.There was a significant difference between the two groups（P<0.05）.2 cases of bleeding events occurred in clopidogrel group during the follow-up period of the 3rd month and there was 1 new case of mild bleeding.6 cases of bleeding events occurred in ticagrelor group during the follow-up period of the 3rd month and there were 3 new cases including 2 cases of mild bleeding eventsand 1case of major intracranial hemorrhage.There were significant differences between the two groups in new cases and the overall cases（P<0.05）.6 cases of bleeding events occurred in clopidogrel group until the 12th month,there were 4 new cases including 3 cases of mild bleeding and 1case of major gastrointestinal hemorrhage.10 cases of bleeding events occurred in ticagrelor group until the 12th month,there were 4 new cases of mild bleeding.There was no significant difference between the two groups in new cases（P>0.05）,while there was a significant difference between the two groups in the overall cases（P<0.05）.6.Compared with dyspnea events of patients between the two groups after PCI on the 1st month,3rd month and 12th month:2 cases of dyspnea occurred on the 1st monthin clopidogrel group including 1 case of mild dyspnea and 1 case of moderate dyspnea.9 cases of dyspnea occurred on the 1st monthin ticagrelor group including 6 cases of mild dyspnea,2cases of moderate dyspnea and 1 case of severe dyspnea.There was a significant difference between the two groups（P<0.05）.Total 3 cases of dyspnea occurred during the follow-up period of the 3rd month in clopidogrel group including1 new case of mild dyspnea.Total 12cases of dyspnea occurred during the follow-up period of the 3rd month in ticagrelor group including 3 new cases of mild dyspnea.There were significant differences in new cases and in the overall cases between the two groups（P<0.05）.Total 4 cases of dyspnea occurred until the12th monthin clopidogrel group including1 new case of mild dyspnea.Total 14 cases of dyspnea occurred until the12th month in ticagrelor group including 1 new case of mild dyspnea and 1 new case of moderate dyspnea.There was no significant difference in new cases（P>0.05）while there was a significant difference in the overall cases between the two groups（P<0.05）.7.Compared with the concentrations of hs-CRP,IL-2 and IFN-γbefore PCI（before taking the medicine）,on the 1st day,on the 7th day,on the 30th day and on the 90th day after PCI in the two groups:There was no statistical difference in the concentrations of hs-CRP,IL-2 and IFN-γbefore PCI between the two groups（P>0.05）.The concentrations of hs-CRP,IL-2 and IFN-γon the1st day after PCI in the two groups were higher than those before PCI（P<0.05）while there was no significant difference between the two groups（P>0.05）.The concentrations of hs-CRP,IL-2 and IFN-γon the 7th day after PCI in the two groups increased than those on the 1st day after PCI（P<0.05）,the clopidogrel group increased higher than the ticagrelor group,there was a significant difference between the two groups（P<0.05）.The concentrations of hs-CRP,IL-2 and IFN-γon the 30th day after PCI in the two groups were significantly lower than those on the 7th day after PCI（P<0.05）,the decrease was more obvious in the ticagrelor group,there was a significant difference between the two groups（P<0.05）.The concentrations of hs-CRP,IL-2 and IFN-γon the 90th day after PCI in the two groups were lower than those on the 30th day after PCI（P<0.05）,the decrease in the ticagrelor group was more obvious,there was a significant difference between the two groups（P<0.05）.8.The variation tendency of the concentrations of hs-CRP,IL-2 and IFN-γin the two groups:The concentrations of hs-CRP,IL-2 and IFN-γin the two groups increased after PCI and reached a higher level on the 7th day.The concentrations decreased significantly on the30th day and decreased more significantly on the 90th day after PCI,especially in the ticagrelor group.Conclusion:1.Double dose of clopidogrel（150 mg,qd）and routine dose of ticagrelor（90 mg,bid）both have significant effectson platelet inhibition in ACS patients with CYP2C19intermediate metabolizer（CYP2C19*1/*2,CYP2C19*1/*3）after PCI and the inhibition of ticagrelor was more adequate.2.Ticagrelor can reduce the incidence of MACEs without increasing the risk of major bleeding in ACS patients on the 1st month,3rd month and 12th month after PCI,while small bleeding events increased and the incidence of dyspnea events were also higher than that of the clopidogrel group.3.The anti-inflammatory and more stronger and directeranti-platelet effects of ticagrelor may induce the better effect in ACS patients with CYP2C19 intermediate metabolizer（CYP2C19*1/*2,CYP2C19*1/*3）after PCI.4.Ticagrelor has stronger anti-platelet effect than clopidogrel which was more beneficial to the prognosis of patients with ACS patients after PCI and worthy of clinical application.5.Detecting CYP2C19 genotype and selecting anti-platelet drug according to the results of the testis more beneficial to the prognosisin ACS patients undergoing PCI.It would promote the extensive implementation of precision medicine in clinical practice. |
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