| Background and Objectives: Acute coronary syndromes (ACS) is one of the most severe diseases threatening human healthy. Percutaneous coronary intervention (PCI) has become the most important treatment of revascularizations for the patients with ACS. Antiplatelet treatment with aspirin and clopidogrel is recommended for patients undergoing coronary stenting to prevent acute or subacute stent thrombosis. Statins, a category of lipid lowering drug, has been proven possessing multiple treatment mechanisms including stabilizing coronary atherosclerotic plaque, counteracting inflammatory factors, improving endothelium functions and inhibiting thrombosis. Statins, as well as clopidogrel, is wildly used in perioperative period of PCI for patients with ACS, so co-administration of clopidogrel and statins is common in current clinical practice. However, Lau et al. claimed in their research paper published in Circulation 2003 that atorvastatin attenuated the antiplatelet function of clopidogrel when atorvastatin and clopidogrel were co-administrated. Clopidogrel, a prodrug, must be activated by cytochrome P450(mainly CYP3A4) to a metabolite that inhibits ADP-induced platelet aggregation. Atorvastatin is mainly metabolized by CYP3A4, too. So the mechanism of the possible drug-drug interaction between clopidogrel and atorvastatin was considered as the competitive inhibition. This viewpoint caught most of cardiologists'attention soon after it was introduced. However, results from following series of trials with small sample were not consistent with whichof Lau's.This openlabeled, randomized and controlled study aimed at evaluating the effects of drug-drug interaction between statins (atorvastatin or pravastatin) and clopidogrel on platelet activation and aggregation function in patients with ACS undergoing coronary stenting.Methods: Between April and December 2006, a total of 150 hospitalized ACS patients undergoing coronary stenting were randomized to receive atorvastatin (n=50), pravastatin(n=50) or no statin (n=50) treatment. Inclusion criteria were the patients with ACS (unstable angina pectoris, no-ST-segment elevation myocardial infarction or ST-segment elevation myocardial infarction) undergoing coronary stenting. Exclusion criteria included tendency of hemorrhage,active digestibility ulcer, cerebral vascular accidence within 1 year, counterindication of antiplatelet or anticoagulation, statins medication within 1 month and administration of glycoproteinⅡb/Ⅲa receptor inhibitor or cilostazol during perioperative period. All patients received standard antiplatelet treatment including aspirin 300mg/d and a 300mg clopidogrel loading dose followed by a maintenance dose of 75mg/d. The expressions of platelet CD62P and PAC-1 and the maximal platelet aggregation rate (MPAR) induced by 20μmol/L ADP were measured at day 1 (baseline) and day 3 after stenting. Treatment of statins started just after the first measurement of platelet function.Results: The baseline clinical characteristics did not differ significantly among three groups. There were no significant differences in the baseline level of CD62P, PAC-1 and MPAR at the first day after stenting among atorvastatin group, pravastatin group and no statin group, CD62P [(16.8±15.54)%vs.(13.05±10.07)%vs.(14.04±9.46)%], PAC-1[(70.28±17.39)%vs. (63.17±18.60)%vs.(69.33±18.44)%] and MPAR[(54.84±17.99)%vs.(57.93±18.84)%vs. (49.44±20.47)%]( all P>0.05).After 3-day statin treatment, the changes of CD62P[(4.69±16.78)%vs.(1.35±10.86)%vs.(2.97±10.21)%],PAC-1[(12.78±22.07)%vs. (8.01±21.23)% vs. (10.65±21.39)%] and MPAR [(5.44±18.68)% vs.(7.15±19.59)%vs.(3.76±23.42)%] among three groups were not significantly different (all P>0.05). And subgroup analysis for patients with acute myocardial infarction(AMI) showed that the baseline clinical characteristics did not differ significantly among three subgroups,CD62P [(18.67±17.51)% vs.(15.36±11.22)%vs.(13.61±8.30)%],PAC-1[(69.03±18.35)%vs.(65.16±17.84)% vs.(67.98±18.25)%]and MPAR [(56.05±17.86)%vs.(60.25±21.38)%vs. (52.35±22.71)%](all P>0.05). And ?CD62P[(7.50±19.35)% vs.(3.24±11.18)% vs. (2.53±8.87)%],?PAC-1[(13.40±24.62)%vs.(11.28±19.90)%vs.(10.11±21.29)%] and ?MPAR[(7.56±19.11)% vs. (7.87±23.60)% vs. (6.75±23.30)%] in patients with AMI were also not of significant difference among three groups (all P>0.05).Conclusion: Neither atorvastatin nor pravastatin is found to attenuate the antiplatelet function of clopidogrel in early period of combined therapy for ACS patients undergoing coronary stenting. However, large-scale randomized clinical trials are needed to confirm the long-term clinical outcomes of the combined treatment of clopidogrel and different statins. Whether a higher dose of atorvastatin would affect antiplatelet functions of clopidogrel is need to be investigated by large-scale randomized clinical trials, too.
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