瑞舒伐他汀和阿托伐他汀在急性冠脉综合症中对氯吡格雷抗血小板活性的对比研究

目的：在急性冠脉综合征（acute coronary syndromes，ACS）的治疗中，抗血小板治疗及调脂治疗是最基础的治疗方案。近来有学者提出，氯吡格雷和他汀类药物都经过细胞色素CYP3A4途径代谢，二者因存在竞争性抑制，有可能降低氯吡格雷抗血小板的活性。本试验将针对阿托伐他汀及瑞舒伐他汀进行研究。方法：选择急性冠脉综合症的患者42例，所有患者均接受氯吡格雷治疗（负荷剂量300mg，维持剂量75mg／d）。随机分配为A、B两组，A组（n=20）服用阿托伐他汀治疗（20mg／d），B组（n=22服用瑞舒伐他汀治疗（10mg／d）。分别于氯吡格雷服用前、服药治疗后3天、服药治疗后7天后采静脉血送检，测定ADP（10μmol／L）诱导的血小板聚集率。结果：阿托伐他汀组（A组）及瑞舒伐他汀组（B组）相比，服用氯吡格雷前ADP诱导的血小板聚集率基线值无统计学差异。服用氯吡格雷3日及7日后，ADP诱导的血小板聚集率明显降低，（3．85±2．58）vs（3．09±2．27），（0．65±0．88）vs（1．05±0．95），P〉0．05，无明显统计学差异。结论：氯吡格雷的确可以降低血小板的活性。同时，短期之内氯吡格雷的抗血小板活性未受到他汀类的影响。包括经过CPY3A4途径的他汀，如阿托伐他汀。

The Influence of Statins on Platelet Inhibition of Clopidogrel in Patients with Acute Coronary Syndromes

Objective： Antiplatelet treatment is fxequently used in high-risk patients with acute coronary syndromes （ACS） who are also often treated with statins. Some scholars indicated that, clopidogrel and statins were both metabolized through cytochrome CYP 3A4, but clopidogrel antiplatelet activity may be reduced due to the competitive inhibition. The effects of atorvastatin and rosuvastatin were compared in this study. Methods： 42 patients diagnosised as acute coronary syndrome were selected. All patients received treatment with clopidogrel （loading dose of 300 mg, maintenance dose of 75 mg/d）, and were randomly assigned to the groups A, B, Group A （n=20） was taken atorvastatin treatment （20 mg/d）, Group B （n=20） was taken rosuvastatin treatment （10 mg/d）. Platelet aggregation induced by adenosine diphosphate （ADP） at 10 ~mol/L was measured by impedance method. Results： Compared atorvastatin group （Group A） with rosuvastatin group （Group B）, there are no significant difference in ADP-induced platelet aggregation baseline values before taken clopidogrel. After clopidogrel therapy for 3 days and 7 days, ADP-induced platelet aggregation was significantly reduced （3.85 ± 2.58 vs 3.09 ±2.27, 0.65±0.88 vs 1.05±0.95; P〉0.05, no statistically significant difference）. Conclusion： Clopidogrel can reduce indeed platelet activity. Meanwhile, the short term antiplatelet activity of clopidogrel is not subject to the influence of statins, including statin metabolized through CPY3A4 pathway, such as atorvastatin.