Real-world Study For Different Clopidogrel Loading Doses On Platelet Function In Patients With Acute Coronary Syndrome

Objective: Acute coronary syndrome(ACS) includes unstable angina pectoris, non-ST segment elevation myocardial infarction and ST segment elevation myocardial infarction. Their common physiopathologic mechanism is, owing to stimulation of inflammation, abnormal activation of platelet and mechanic stress, the ruptured unstable plaque and the formation of acute thrombus result in different degreed blockage in coronary artery and acute myocardial ischemia. Of all, platelet aggregation and platelet activation is very important in the formation of thrombus. P-selectin is a specific index that reflects the activation of platelet. This study is designed to compare different loading doses of clopidogrel if they are differences in the effect on the function of platelet in patients with percutaneous coronary intervention(PCI) before undergoing PCI by testing platelet aggregation and P-selectin level, and so to provide theoretical basement for the proper loading dose of clopidogrel for preoperation in emergency or in schedule.Methods:The study population has included 65 patients with ACS, which are confirmed coronary heart disease by coronary arteriography. Their average age is 59.4±12.7 years old. The 65 patients is classified into three study groups randomly according to the given loading dose of clopidogrel, they are respectively 300 mg group,450 mg group and 600 mg group. At the same time, all study groups are received 300 mg loading dose aspirin, followed by 75 mg clopidogrel and 100 mg aspirin daily. Control group are 20 patients including 7 patients with stable angina pectoris and 13 with old myocardial infarction. The control group are received 75 mg clopidogrel and 100 mg aspirin daily. Platelet aggregation and the expression of P-selectin in study groups are tested before drug administered (0h) and in 2h, 4h, 6h, 24h, 72h after administered. The same indexes in control group are tested before administered(0h) and in 6h, 24h, 72h after administered. Platelet aggregation is tested by the optical aggregometry method, and the expression of P-selectin is tested by enzyme-linked immunosorbent assays (ELISA).Results: 1. Platelet aggregation and the expression of P-selectin of the study groups are obvious higher than that of control group before administered(P <0.05).2.①Platelet aggregation after administered of the study groups at all tested points are lower than that before administered. Platelet aggregation in 6h is lowest at all tested points of the first 24 hours.②Compared with 300 mg group, 450 mg group and 600 mg group have higher inhibition of platelet aggregation(P<0.05)in 2h, 6h and 24h;The inhibition of platelet aggregation of 450 mg group and 600 mg group are approximal at all tested points.3.①The expression of P-selectin of the study groups after administered at all tested points are lower than that before administered. The expression of P-selectin at all tested points is descended in trend.②Compared with 300 mg group,450 mg group and 600 mg grouphave higher inhibition of the expression of P-selectin(P <0.05)in 2h,6h and 24h;The expression of P-selectin of 450 mg group and 600 mg group are approximal at all tested points.4.①As the time of the use of clopidogrel being longer, clopidogrel responsiveness improves in trend, the inhibition rate of platelet aggregation of control group and study groups can both reach optimal level of 30%.②There are 2 patients in group 300 mg,2 in group 450 mg,1 in group 600 mg whose inhibition rate of platelet aggregation is always lower than 10%.It is means that some patients in each study group is always nonresponsive after clopidogrel Loaded.Conclusions:1.Compare with stable angina pectoris and old myocardial infarction, platelet activation of ACS is more obvious.2.Compare with 300 mg group, 450 mg group and 600 mg group have more effective platelet inhibition, moreover, the effect of platelet inhibition of 450 mg group and 600 mg group are approximal. To reduce possibly adverse reaction as bleeding, 450 mg loading dose can be use as a routine dose of clopidogrel before emergency PCI or scheduled PCI.3.Compare with study groups, maintaining dose clopidogrel (75mg/d) takes effect more slowly, but can achieve optimal result in 72 hours too.