Study On Antiplatelet Efficacy And Its Effect On Recent Adverse Events Of Pre-PCI Dual Antiplatelet Therapy With Different Durations In Chinese Elderly Patients With ACS

Background: The dual antiplatelet therapy(DAPT)of aspirin combined with clopidogrel is still the commonly used antithrombotic regimen in patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Combined with the pharmacokinetic and pharmacodynamic characteristics of aspirin and clopidogrel,the antiplatelet efficacy is related to the dosage and time of medication.Clinically,the medication of patients with ACS was different when they were admitted to hospital,and the duration of DAPT was different before PCI.Especially for patients undergoing emergency PCI,whether adequate antiplatelet effect can be achieved before PCI and the occurrence of recent adverse events after PCI need to be verified by relevant clinical studies.In addition,elderly patients with ACS have both high risk of thrombosis and bleeding.Combined with clinical individual differences and clopidogrel genotypes,platelet function test was applied to evaluate the antiplatelet efficacy and recent adverse events under different drug regimens,which will provide support for the selection of antiplatelet regimen before PCI.Objective:To explore the influencing factors of platelet aggregation rate(PAR)within 24 hours before PCI in Chinese elderly patients with ACS.To explore the antiplatelet efficacy before PCI and the short-term adverse events(within 7 days and within 3 months after PCI)in patients with different administration of "aspirin+clopidogrel".Three clinically common administration of DAPT were included in our study,respectively:(1)aspirin with daily dose of 100 mg and clopidogrel with 75mg/day were administered regularly for more than 7 days before PCI;(2)before PCI,aspirin with daily dose of 100 mg was used regularly for more than 7 days,and 300 mg clopidogrel for the first time and then clopidogrel75mg/day for maintenance;(3)before PCI,aspirin and clopidogrel were given 300 mg for the first time,followed by routine dose maintenance.Methods: This is a retrospective and observational study.Using the electronic medical record management system of Huazhong Fuwai Hospital,we selected elderly patients(age≥60 years old)who were treated with “aspirin + clopidogrel”DAPT and underwent PCI in CHD ward of the hospital from March 01,2019 to March 01,2020.According to the inclusion and exclusion criteria,182 patients were included.Detailed clinical medical records were collected,and patients were followed up to 3 months post-PCI by reviewing follow-up records and telephone enquiries.Patients were divided into an effective group(PAR<55%)and an ineffective group(PAR≥55%)according to the maximum PAR induced by adenosine diphosphate(ADP-PAR)within 24 hours before PCI.SPSS 25.0 statistical software was used to compare the general characteristics of two groups of patients,clinical data and test results between the two groups.Further,multivariate Logistic regression was performed to analyze the independent influencing factors of preoperative PAR.ROC curves were used to analyze the predictive value of indicators on PAR.The efficiency rate of PAR and adverse events of patients with different administration methods of DAPT were analyzed.P<0.05 indicated that the difference was statistically significant.Results:1.Univariate analysis showed that hyperlipidemia,clopidogrel metabolic genotypes,DAPT administration before PCI had statistically significant differences between the ADP-PAR effective group and the ineffective group(P<0.05).And there were significant differences in PLT,MPV,PCT,LDL-C,Hb A1 c and UA between the two groups(P < 0.05).2.Multivariate Logistic regression analysis shows that hyperlipidemia(OR=2.654,95%CI1.061～6.637,P=0.037),admission test of PLT(OR=0.973,95%CI 0.964～0.983,P<0.001)and MPV(OR=0.522,95%CI 0.362～0.753,P=0.001)were independent predictors of preoperative ADP-PAR.Compared with the poor metabolizer of clopidogrel metabolic gene,the ADP-PAR was more effective(P<0.05)in extensive metabolizers.Patients with aspirin and clopidogrel regularly administered for more than 7 days had a more effective antiplatelet efficacy before PCI compared with loading dose administration(P<0.05).3.Receiver operating curve(ROC)analysis showed that the levels of PLT,MPV and UA had a certain predictive value on the inefficiency of preoperative ADP-PAR.The predicted AUC of the inefficiency of ADP-PAR within 24 H before PCI was 0.621(95%CI 0.539～0.703,P=0.005),the optimal cut-off point was 0.187,and the optimal cut-off value of MPV was 10.35 f L.4.Among the three groups with different administration methods of “aspirin+clopidogrel”DAPT,there were statistically significant differences in ADP-PAR before PCI,and adverse events within 7 days after PCI(P<0.05).There was no significant difference in adverse events within 3months after PCI(P>0.05).Moreover,the 1st method(aspirin and clopidogrel regularly administered for more than 7 days)had a higher efficiency of PAR before PCI and a lower incidence of adverse events within 7 days after PCI.5.Patients with different phenotypes of clopidogrel metabolic gene had statistically significant differences in the incidence of adverse events within 7 days and within 3 months after PCI(P<0.05).And extensive metabolizers of clopidogrel metabolic gene had a lower incidence of recent postoperative adverse events than intermediate and poor metabolizer.Conclusions:1.In elderly patients with ACS treated with aspirin and clopidogrel,the level of ADP-induced PAR before PCI is related to a variety of factors.Hyperlipidemia,high levels of PLT,MPV,Hb A1 c and UA independently affected the efficiency of PAR.2.Compared with patients with pre-PCI loading dose administration,patients with regular“aspirin+clopidogrel”DAPT administration for more than 7 days before PCI had better antiplatelet efficacy and a lower incidence of adverse events within 7 days after PCI.3.Compared with intermediate or poor metabolizers,clopidogrel extensive metabolizers had a lower incidence of recent adverse events after PCI.