Blagojevic Ana, Delaney Joseph A C, Lévesque Linda E, Dendukuri Nandini, Boivin Jean-Francois, Brophy James M
Department of Medicine, McGill University Health Center, Quebec, Canada.
Pharmacoepidemiol Drug Saf. 2009 May;18(5):362-9. doi: 10.1002/pds.1716.
Clopidogrel is an antiplatelet drug that is prescribed after percutaneous coronary intervention (PCI) to prevent stent thrombosis. Previous studies have suggested that some statins may inhibit the antiplatelet effects of clopidogrel via competitive metabolism of its activating enzyme cytochrome P450 3A4 (CYP3A4).
To investigate a possible interaction between statins and clopidogrel after a PCI procedure in a population-based cohort study.
A population-based cohort study was carried out between January 2001 and December 2004 using the health insurance databases from Quebec, Canada. The primary endpoint was a composite of death from any cause, myocardial infarction (MI), unstable angina, repeat revascularization and cerebrovascular events. PCI patients >or= 66 years of age were followed from their initial post-discharge clopidogrel prescription until the earliest of study endpoint occurrence, end of clopidogrel exposure or end of study (90 days post discharge). Time-dependent Cox regression analysis was performed.
We identified 10491 patients who were prescribed clopidogrel post-PCI and 43.5% were also prescribed statins at the baseline discharge. During 1793 patient years of follow-up, 623 composite endpoints were observed. Compared to the reference group (non-CYP3A4-metabolized statins), the co-prescription of CYP3A4-metabolized statins (hazard ratio (HR) 1.16, 95% confidence interval (CI) 0.91-1.47), or no statin use (HR 1.22, 95%CI 0.93-1.59) were not statistically associated with an increase in adverse outcomes.
In this PCI cohort, the association of clopidogrel with CYP3A4-metabolized statins did not demonstrate an increased early risk of adverse cardiovascular events, although a small risk could not be completely excluded.
氯吡格雷是一种抗血小板药物，常用于经皮冠状动脉介入治疗（PCI）后预防支架血栓形成。此前的研究表明，某些他汀类药物可能通过竞争性代谢其激活酶细胞色素P450 3A4（CYP3A4）来抑制氯吡格雷的抗血小板作用。
在一项基于人群的队列研究中，调查PCI术后他汀类药物与氯吡格雷之间可能存在的相互作用。
2001年1月至2004年12月期间，利用加拿大魁北克省的医疗保险数据库进行了一项基于人群的队列研究。主要终点是任何原因导致的死亡、心肌梗死（MI）、不稳定型心绞痛、再次血管重建和脑血管事件的综合结果。年龄≥66岁的PCI患者从出院后首次开具氯吡格雷处方开始随访，直至最早出现研究终点、氯吡格雷暴露结束或研究结束（出院后90天）。进行了时间依赖性Cox回归分析。
我们确定了10491例PCI术后开具氯吡格雷处方的患者，其中43.5%在基线出院时也开具了他汀类药物。在1793患者年的随访期间，观察到623个综合终点。与参照组（非CYP3A4代谢的他汀类药物）相比，联合使用CYP3A4代谢的他汀类药物（风险比（HR）1.16，95%置信区间（CI）0.91-1.47）或未使用他汀类药物（HR 1.22，95%CI 0.93-1.59）与不良结局增加无统计学关联。
在这个PCI队列中，氯吡格雷与CYP3A4代谢的他汀类药物联合使用并未显示出早期不良心血管事件风险增加，尽管不能完全排除小风险。
