A Comparative Study On The Efficacy And Safety Of Ticagrelor And High Maintenance Dose Clopidogrel In Acute Coronary Syndrome Patients With Inadequate Response To Clopidogrel

Objective: This trial is aimed at comparaing the efficacy and safety of ticagrelor and high maintenance dose clopidogrel in acute coronary syndrome(ACS) with inadequate response to clopidogrel.Methods: In this prospective, randomized and controlled study, a total of 77 patients(58males and 19 females) who had been diagnosed as ACS with inadequate response to clopidogrel in the Second Hospital of Hebei Medical University from February 2015 to December 2015 were enrolled. Inadequate response to clopidogrel was defined as absolute reduction of platelet aggregation rate<30% or platelet aggregation rate>70%. Patients were all performed CAG and PCI in hospital. Patients with bleeding diathesis, thrombocytopenia, recent stroke, severe hepatic and renal dysfunction, women with pregnancy and lactation, received GPⅡb/Ⅲa receptor antagonist therapy and hypersensitiveness of clopidogrel or ticagrelor were excluded. Eligible patients were randomly assigned to two groups, the high maintenance dose group(n=37, 150 mg clopidogrel per day) and the ticagrelor group(n=40, 90 mg ticagrelor twice a day). We collected detailed clinical informations including: age, gender, risk factors, Body Mass Index(BMI), pathological changes of coronary artery and the basic medical treatment.We measured the platelet aggregation rate of the two groups at the time of baseline, the third day, the first month, and the third month after treatments, the other platelet-related parameters were measured including platelet(PLT), Mean platelet volume(MPV), platelet distribution width(PDW) at the same time. Besides, the markers of platelet activation Human P-selectin(CD62P) and thromboxane A2(TXA2) were also recorded to compare. The incidence of major adverse cardiac events(MACE) and the adverse events between two groups were followed up for three months. All clinical datas were analyzed with SPSS 20.0. The variables were presented as the means and the SD. Differences between the two groups means were assessed with the t test or ranks test. The χ2 analysis or the Fisher exact test were used to test differences between proportions. P Value of less than 0.05(2-tailed) was considered to be statistically significant.Results:1 There were no significant differences between both groups in baseline characteristics, including gender distribution, age, risk factors(hypertension, diabetes mellitus, hyperlipidermia, smoking history), BMI, GRACE score, CRUSADE score, basic medication, pathological changes of coronary artery, angiographic and procedural characteristics( P>0.05).2 There were no significant differences in baseline levels of platelet aggregation rate(PAR) among the two groups [(79.38±11.20)% vs.(73.97±12.74)%, P>0.05]. For both groups, the PAR significantly decreased at each time point(P<0.001). Besides, compared to clopidogrel group, the PAR of ticagrel group was lower at the third day, the first month and the third month: [(25.92±10.31)% vs.(37.95±11.63)%, P<0.001], [(28.02±14.61)% vs.(30.64±10.73)%, P<0.001], [(37.17±11.11)% vs.(36.80±7.26)%, P<0.001]. The change of the PAR of the ticagrelor group was larger than the high maintenance dose clopidogrel group at the third day, the first month and the third month: [(53.46±14.92)% vs.(36.02±12.65)%, P<0.001], [(51.36±18.8)% vs.(33.70±12.56)%, P<0.001], [(48.74±15.68)% vs.(37.17±11.11)%, P<0.001].3 The baseline levels of PLT, PDW, and MPV were similar between the two groups(P>0.05), and there were no significant differences to the baseline levels of PLT, PDW, and MPV at each time point.Besides, Compared to clopidogrel group, the values of PLT, PDW, MPV at different time were also not significantly different(P>0.05) but the level of MPV in ticagrel group had a tendency to decrease.4 There were also no significant differences of the platelet activation markers CD62p(P=0.825) and TXA2(P=0.233) between the two groups. Hower, it was lower in ticagrelor group than that in clopidogrel group at the third day [(5.47±1.03)ng/ml vs.(8.02±1.45)ng/ml, P<0.001] while the CD62 P concentrations of the two groups significantly decrease to the baseline levels(P<0.001). However, there were no significant differences in TXA2 concentrations between the two groups or the same group at each time point.5 During 3-month follow-up, there were 3 cases of cardiovascular adverse events, 3 cases of Minor bleeding and 0 case of dyspnea in high maintenance dose clopidogrel group; there were 1 case of cardiovascular adverse events, 4 cases of minor bleeding, 4 cases of dyspnea and 1case of Bradycardia in ticagrelor group, not resulting in a statistically difference(P>0.05).Conclusions:1 Routine maintance dose ticagrelor and high maintentace dose clopidogrel could obviously suppress platelet reactivity, and routine maintenance dose ticagrelor significantly decrease platelet reactivity.2 Ticagrelor could decrease the expression of CD62 P and strongly inhibit the activation of palatelet more significantly than Clopidogrel.3 Comparaing with high maintenance dose clopidogrel, there is a tendency that ticagrelor could reduce the incidence of MACE,but not increase the hemorrhage events.