Antiplatelet Therapy In Acute Coronary Syndrome Patients Undergoing Coronary Stenting With Aspirin Intolerance

Objective Antiplatelet therapy significantly decreases the incidence of thrombotic events after coronary stenting. The reason of increased risk of thrombotic events in patients with acute coronary syndromes is antiplatelet resistance. There was no uniform diagnosis standard of antiplatelet resistance and effective therapeutic methods. The present study was aimed to investigate the clinical value of laboratory diagnosis antiplatelet resistance by WBIA, to analyze the relationship between antiplatelet resistance and clinical risk factors, and to explore the efficacy and safety of optimal anitplatelet therapy in managing antiplatelet resistance and aspirin intolerance with underwent percutaneouscoronary intervention(PCI).Methods1. A total of 300 consecutive ACS patients underwent PCI were enrolled. ADP and AA induced platelet aggregation(IPA) were assayed by whole blood impedance aggregometry(WBIA)before and 7days after administration of antiplatelet agents. To analyze the relationship between antiplatelet resistance and clinical risk factors. Overall patients were followed for one year. The clinical endpoints were MACCE. Both the SYNTAX score and the incidence of clinical endpoints were compared between the two groups.2. A total of 86 consecutive ACS patients with Clopidogrel resistance underwent PCI were enrolled. 51 patients were given aspirin 100 mg/d a day plus ticagrelor 90 mg twice a day as aspirin group; other 36 patients with aspirin intolerance received cilostazol 100 mg twice a day plus ticagrelor 90 mg twice a day as cilostazol group. The platelet aggregation was measured by WBIA at 7 and 14 days after therapy. In the assay, platelet aggregation was activated by AA and COL. Overall patients were followed for one year. The clinical endpoints were MACCE and bleeding events. Both the platelet aggregation and the incidence of clinical endpoints were compared between the two groups.3. A total of 148 consecutive ACS patients(body weights ≤ 65kg) with aspirin intolerance underwent PCI were enrolled and randomly divided into four groups. The group were given cilostazol 50 mg twice a day plus clopidogrel 75mg/d as CC50 mg group. CC100 mg group were given cilostazol 100 mg twice a day plus clopidogrel 75mg/d. TC50 mg group were given cilostazol 50 mg twice a day plus standard ticagrelor 90 mg twice a day and TC100 mg group were given cilostazol 50 mg twice a day plus standard ticagrelor 90 mg twice a day. Overall patients were followed for one year. The clinical endpoints were MACCE and bleeding events. Both the platelet aggregation and the incidence of clinical endpoints were compared between the four groups.Results1.The rate of aspirin resistance incidence was 26%, The rate of clopidogrel resistance was28.7%.The SYNTAX score were similar between the two groups. AR group TIMI risk score was significantly higher than NAR group(3.53±1.34 比 1.23±1.09,P<0.001)。With the increase of TIMI risk score, the incidence of AR is rising. ROC curve analysis showed TIMI risk score was2.5 timeshare cut off value of AR, CR anticipation with moderate diagnostic value, the area under the ROC curve were 0.760 and 0.835. Multivariate analysis demonstrated that diabetes,history of stroke, positive Tn T, hypercholesterolemia, HCY > 15μmol/L and RDW CV(%) >15% were predictors of AR. Diabetes, history of stroke, troponin-positive, male,hypercholesterolemia, HCY>15μmol/L and RDW CV(%)>15% were independent risk factor of CR. SYNTAX score of no resistance group significantly lower than AR and CR( 10.21±9.79VS18.32±18.78 、 19.57±11.32, P=0.012)。 The incidence of MACCE of no resistance group was significantly lower than AR group’s and CR group’s(P=0.013).2. According to the platelet aggregation test by WBIA at 7 and 14 days after therapy, the AA-induced impedance values of aspirin group were lower than values of cilostazol group(0.09±0.13VS1.56±1.86,0.45±0.21VS1.73±1.79, P=0.001,P=0.002). After 3 months and one year follow up incidence of MACCE were not significantly different between the two groups(P=0.387, P=0.158). The total bleeding events rates was no significant differences between the two groups(P=0.096). Nevertheless, the total bleeding events rates in cilostazol group was significantly lower than the aspirin group after 3 months(P=0.048).3.According to the platelet aggregation test at 7 days and 30 days after therapy, the ADP-induced and AA-iuduced impedance values of TC100 mg group were lower than values of other groups in ACS patients(body weights ≤ 65kg) with aspirin intolerance underwent PCI(P<0.05). After 6months follow up incidence of MACCE was not significantly different between the four groups(P=0.930). After 6 months follow up 12 patients suffered from bleeding. The incidence of leeding events in TC100 mg group was significant higher than the other groups(P=0.014). After6 months of results of echocardiography(LVEF%、VSD、LVEDD) were no significant differences between four groups(P>0.05). Nevertheless, results of LVEF(%)in all groups were better than before treatment(P=0.022、0.031、0.019、0.028).Conclusions The method of platelet aggregation measured by WBIA has some clinical reference valulaboratory diagnosis. In ACS patients with clopidogrel resistance underwent PCI with asintolerance, cilostazol plus ticagrelor is a safe and efficacious therapy regimen. In ACS pat(body weights ≤ 65kg) with aspirin intolerance underwent PCI, cilostazol 50 mg twice a day ticagrelor is a safe and efficacious therapy regimen. It is not harm to renal about that ticagplus cilostazol antiplatelet therapy in ACS patients(body weights ≤ 65kg) with asintolerance underwent PCI.