Comparison of ticagrelor and high-dose clopidogrel on the platelet functions in patients with inadequate response to clopidogrel.
OBJECTIVE
To evaluate the effects of ticagrelor and high-dose clopidogrel on the platelet functions in patients with inadequate response to clopidogrel.


METHODS
In this prospective, randomized and controlled study, patients who had been diagnosed as acute coronary syndrome (ACS) with inadequate response to clopidogrel in the Second Hospital of Hebei Medical University from July 2015 to June 2016 were enrolled. Inadequate response to clopidogrel was defined as absolute reduction of platelet aggregation rate (PAR) <30% or PAR >70%. Eligible patients were randomly assigned to two groups, the high-dose group and the ticagrelor group. Clinical information and intervention protocols were compared. The PAR of the two groups were measured at the time of baseline, the 24thhour, 72ndhour, and the 7thday after treatments, the other platelet-related parameters were measured including platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW) at the same time points. 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 side effects between two groups were followed up for three months.


RESULTS
A total of 74 patients were finally enrolled, 38 of whom were assigned to the ticagrelor group and the rest of them to the high-dose clopidogrel group. The baseline clinical and procedural characterists were similar. There were no significant differences in baseline levels of PAR between the two groups [(79.38±11.20)% vs. (73.97±12.74)%, P>0.05]. For both groups, the levels of PAR significantly decreased at each time point (P<0.001). Besides, the levels of PAR in ticagrelor group were lower than those in high-dose clopidogrel group at the 24thhour, 72ndhour and 7thday after treatments: [(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 baseline levels of platelet related parameters were similar between the two groups (P>0.05), and there were no significant differences in the levels of PLT, PDW, and MPV at the 24thhour, 72ndhour and 7thday. It was lower in ticagrelor group than that in clopidogrel group at the 24thhour [(5.47±1.03) ng/ml vs. (8.02±1.45) ng/ml, P<0.001] while the CD62P concentrations in the two groups significantly decreased comparing to the baseline levels (P<0.001). During 3-month follow-up, the incidences of MACE and side effects were not significantly different between the two group.


CONCLUSIONS
ticagrelor could further decrease levels of platelet aggression rate and CD62p compared with high-dose clopidogrel, without serious side effects.
Department of Cardiology, The Second Hospital of Hebei Medical University Shijiazhuang 050000, China.
Xinshun
X
Gu
Department of Cardiology, The Second Hospital of Hebei Medical University Shijiazhuang 050000, China.
Xianghua
X
Fu
Department of Cardiology, The Second Hospital of Hebei Medical University Shijiazhuang 050000, China.
Yanbo
Y
Wang
Department of Cardiology, The Second Hospital of Hebei Medical University Shijiazhuang 050000, China.
Wenhui
W
Zhang
Department of Cardiology, The Second Hospital of Hebei Medical University Shijiazhuang 050000, China.
Weize
W
Fan
Department of Cardiology, The Second Hospital of Hebei Medical University Shijiazhuang 050000, China.
Yunfa
Y
Jiang
Department of Cardiology, The Second Hospital of Hebei Medical University Shijiazhuang 050000, China.
Guozhen
G
Hao
Department of Cardiology, The Second Hospital of Hebei Medical University Shijiazhuang 050000, China.
Qing
Q
Miao
Department of Cardiology, The Second Hospital of Hebei Medical University Shijiazhuang 050000, China.
Yi
Y
Li
Department of Cardiology, The Second Hospital of Hebei Medical University Shijiazhuang 050000, China.
Wei
W
Zhi
Ticagrelor; acute coronary syndrome; clopidogrel resistance; human P-selectin; thromboxane A2