Gulec Sadi, Ozdol Cagdas, Rahimov Uzeyir, Atmaca Yusuf, Kumbasar Deniz, Erol Cetin
Department of Cardiology, Ankara University Medical School, Ankara, Turkey.
J Invasive Cardiol. 2005 Nov;17(11):589-93.
A recent ex vivo study suggests that the metabolic activation of clopidogrel is catalyzed by cytochrom P450 (CYP) 3A4 and is competitively inhibited by atorvastatin, but not pravastatin.
To determine whether the incidence of procedure-related myocardial injury, assessed by cardiac troponin T (cTnT) release, is altered when clopidogrel is coadministered with a statin that is predominantly CYP3A4-metabolized.
Of the 211 consecutive patients who underwent coronary stenting after pretreatment with clopidogrel, 114 were receiving a CYP3A4-metabolized statin (59 simvastatin and 55 atorvastatin, Group 1), and 37 were receiving a non-CYP3A4-metabolized statin (30 pravastatin and 7 fluvastatin, Group 2) whereas 60 patients were not taking any statins (Control). All were troponin-negative before the procedure. The overall incidence of postprocedural cTnT positivity (> 0.10 ng/ml) was 30.8%. Group 2 patients were less likely to exhibit cTnT rise relative to Group 1 patients (8% versus 41.6%; p = 0.004) and relative to controls (8% versus 32.5%; p < 0.001). Multivariate analysis identified the use of a non-CYP3A4-metabolized statin before coronary stenting as the sole independent predictor for lower incidence of procedure-related cTnT elevation with estimated Odds ratios of 0.16 relative to no statin therapy (95% CI: 0.04-0.59; p = 0.006) and 0.18 relative to CYP3A4-metabolized statin therapy (95 CI: 0.053-0.637; p = 0.008)
Benefit derived from the preprocedural use of pravastatin and fluvastatin but not atorvastatin and simvastatin suggest that the ex vivo finding of a negative interaction when coadministering a CYP3A4-metabolized statin with clopidogrel may be of clinical significance.
最近一项体外研究表明，氯吡格雷的代谢活化由细胞色素P450（CYP）3A4催化，且受阿托伐他汀竞争性抑制，但不受普伐他汀抑制。
确定当氯吡格雷与主要经CYP3A4代谢的他汀类药物合用时，通过心肌肌钙蛋白T（cTnT）释放评估的与手术相关的心肌损伤发生率是否会改变。
在211例接受氯吡格雷预处理后进行冠状动脉支架置入术的连续患者中，114例接受经CYP3A4代谢的他汀类药物（59例辛伐他汀和55例阿托伐他汀，第1组），37例接受非CYP3A4代谢的他汀类药物（30例普伐他汀和7例氟伐他汀，第2组），而60例患者未服用任何他汀类药物（对照组）。所有患者在手术前肌钙蛋白均为阴性。术后cTnT阳性（>0.10 ng/ml）的总体发生率为30.8%。与第1组患者相比（8%对41.6%；p = 0.004）以及与对照组相比（8%对32.5%；p < 0.001），第2组患者cTnT升高的可能性较小。多因素分析确定，在冠状动脉支架置入术前使用非CYP3A4代谢的他汀类药物是手术相关cTnT升高发生率较低的唯一独立预测因素，相对于未使用他汀类药物治疗，估计比值比为0.16（95%CI：0.04 - 0.59；p = 0.006），相对于经CYP3A4代谢的他汀类药物治疗为0.18（95%CI：0.053 - 0.637；p = 0.008）。
术前使用普伐他汀和氟伐他汀有益，但阿托伐他汀和辛伐他汀则不然，这表明体外研究中关于经CYP3A4代谢的他汀类药物与氯吡格雷合用时存在负性相互作用的发现可能具有临床意义。
