资讯浅译：在脑缺血二级预防中氯吡格雷与他汀类药物的相互作用

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Interaction of clopidogrel and statins in secondary prevention after cerebral ischemia （脑缺血）- a randomized, double-blind, double-dummy crossover-study.
一项随机、双盲、双模拟的试验：在脑缺血二级预防中氯吡格雷与他汀类药物的相互作用
AIMS:
Variability in responsiveness to clopidogrel is a clinical problem in secondary prevention after cerebral ischemia which has been suggested to be linked to competitive metabolization of clopidogrel and cytochrome P450 (CYP) 3A4-oxidated statins such as simvastatin辛伐他汀 We assessed the hypothesis that simvastatin, in contrast to CYP 2C9-metabolized fluvastatin, reduces clopidogrel-mediated platelet inhibition.
目标：氯吡格雷反应的变异性对于脑缺血后的二级预防一直是一个临床不可回避的问题。其变异性被认为与氯吡格雷和他汀类药物，例如辛伐他汀的竞争性代谢。我们的评估假设，相比于经CYP2C9代谢的氟伐他汀，辛伐他汀更能减少由氯吡格雷介导的血小板抑制。
METHODS:
We performed a randomized, double-blind, double-dummy, 2-period crossover-study in 13 patients with cerebral ischemia (8f, 5m), aged 64.1±8.0 years (mean±SD). After a 14-day period in which all patients received 75mg clopidogrel/day, patients additionally received either 20 mg simvastatin/day or 80 mg fluvastatin/day for 14 days. Regimens were crossed over after a 14 day wash-out period and switched regimens were continued for another 14 days. Platelet aggregation（血小板凝集）, clopidogrel active metabolite (CAM) plasma concentrations（氯吡格雷活性代谢物血药浓度） and routine laboratory parameters（常规实验室参数） including prothrombin time （凝血酶原百分比）(PT) Quick percent value were assessed at baseline and following each treatment phase.
方法：我们设计了一项随机、双盲、双模拟，双周期交叉试验。入主13例脑缺血、年龄64.1±8.0岁患者。口服氯吡格雷75mg/天，共服14天，14天洗脱期后，患者另外接受20mg辛伐他汀/天或者80mg氟伐他汀/天14天。血小板聚集、氯吡格雷活性代谢物血药浓度、常规实验室参数包括PT快速百分比分别在基线和每个治疗阶段后被测定。
RESULTS:
Clopidogrel reduced platelet aggregation in all patients as expected. Platelet aggregation and CAM plasma levels were unaltered when simvastatin or fluvastatin was added to clopidogrel. Simvastatin decreased PT Quick percent value (decrease from 109±10.5% to 103±11%, p<0,05) when combined with clopidogrel but there was no such change following treatment with fluvastatin and clopidogrel.
结果：氯吡格雷正如期望一样减少了所有入主患者的血小板聚集。在应用氯吡格雷基础上加入辛伐他汀或氟伐他汀对血小板聚集与CAM的血浆水平没有显著改变。与氯吡格雷联用时，辛伐他汀降低了PT快速百分比（从109±10.5%降到103±11%,），反之氟伐他汀与氯吡格雷联用并没有此种变化。
CONCLUSIONS:
Our data indicate that treatment with CYP 3A4-metabolized simvastatin does not jeopardize clopidogrel-mediated inhibition of platelet aggregation. In co-administration of simvastatin and clopidogrel we observed decrease in PT Quick percent value which could be due to simvastatin-induced reduction of activity of prothrombin fragment 1+2.
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结论：我们的数据表明，使用参与CYP3A4代谢的辛伐他汀不影响氯吡格雷介导的血小板聚集的抑制，同时我们观察到的氯吡格雷对PT快速百分比的减少也许是由辛伐他汀引起的凝血酶原片段1+2的活性的降低造成的。

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