Schroeder Walter S, Ghobrial Linda, Gandhi Pritesh J
Pharmacy and Medicine, Department of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Cooke Hall 317, Buffalo, NY 14260, USA.
J Thromb Thrombolysis. 2006 Oct;22(2):139-50. doi: 10.1007/s11239-006-8670-y.
Aspirin (ASA) and clopidogrel have been identified as standard of care in the prevention of major cardiovascular events. Aspirin irreversibly inhibits the cyclooxygenase-1 (COX-1) enzyme, whereas non-steroidal anti-inflammatory drugs (NSAIDs) reversibly inhibit the COX-1 enzyme. An analysis of the literature revealed a statistically significant decrease in clinical benefit of ASA with concomitant administration of ibuprofen. Another NSAID, diclofenac, showed minimal effect on the inhibition of platelet aggregation when administered with ASA. Furthermore, the selective COX-2 inhibitor, rofecoxib, was not shown to influence the effect of ASA. Clopidogrel is metabolized to an active thiol metabolite by the CYP 3A4 enzyme. Some HMG CoA reductase inhibitors have the ability to inhibit the CYP 3A4 enzyme, which can result in a possible interaction if administered concomitantly with clopidogrel. Studies have demonstrated clopidogrel's platelet inhibition being significantly attenuated by atorvastatin. However in a post-hoc analysis, it was demonstrated that there was no difference in clinical outcomes between patients taking clopidogrel and HMG-CoA reductase inhibitors metabolized by and not metabolized by CYP 3A4. Data suggest that the interaction observed involving clopidogrel and HMG-CoA reductase inhibitors appears to be significant in-vitro. Therefore, practitioners should advise patients receiving chronic aspirin therapy to limit the use of ibuprofen and may consider concomitant administration of clopidogrel with HMG-CoA reductase inhibitors without regard for the drug interaction. The intent of this paper is to review the literature discussing possible mechanisms of drug-induced aspirin and clopidogrel resistance and discuss whether the interactions translate into clinical effects.
阿司匹林（ASA）和氯吡格雷已被确定为预防重大心血管事件的护理标准。阿司匹林不可逆地抑制环氧化酶-1（COX-1）酶，而非甾体抗炎药（NSAIDs）可逆地抑制COX-1酶。文献分析显示，同时服用布洛芬会使ASA的临床益处出现统计学上的显著下降。另一种NSAID双氯芬酸与ASA合用时，对血小板聚集的抑制作用最小。此外，选择性COX-2抑制剂罗非昔布未显示会影响ASA的效果。氯吡格雷经细胞色素P450 3A4（CYP 3A4）酶代谢为活性硫醇代谢物。一些HMG辅酶A还原酶抑制剂有能力抑制CYP 3A4酶，如果与氯吡格雷同时给药，可能会导致相互作用。研究表明，阿托伐他汀会显著减弱氯吡格雷对血小板的抑制作用。然而，事后分析表明，服用氯吡格雷的患者与经CYP 3A4代谢和不经CYP 3A4代谢的HMG辅酶A还原酶抑制剂之间，临床结局并无差异。数据表明，观察到的氯吡格雷与HMG辅酶A还原酶抑制剂之间的相互作用在体外似乎很显著。因此，从业者应建议接受慢性阿司匹林治疗的患者限制使用布洛芬，并且在考虑氯吡格雷与HMG辅酶A还原酶抑制剂同时给药时，可不考虑药物相互作用。本文旨在综述讨论药物诱导的阿司匹林和氯吡格雷抵抗可能机制的文献，并探讨这些相互作用是否会转化为临床效应。
