Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea.
Eur Heart J. 2012 Sep;33(17):2151-62. doi: 10.1093/eurheartj/ehs083. Epub 2012 Apr 16.
CYP3A4-metabolized statins can influence the pharmacodynamic effect of clopidogrel. We sought to assess the impact of switching to a non-CYP3A4-metabolized statin on platelet function among patients receiving clopidogrel and atorvastatin with high on-treatment platelet reactivity (HPR).
Percutaneous coronary intervention (PCI)-treated patients (n= 50) with HPR [20 μM adenosine diphosphate (ADP)-induced maximal platelet aggregation (MPA) >50%] were enrolled during chronic administration of atorvastatin (10 mg/day) and clopidogrel (75 mg/day) (≥6 months). They were randomly assigned to a 15-day therapy with either rosuvastatin 10 mg/day (n= 25) or pravastatin 20 mg/day (n= 25). Platelet function was assessed before and after switching by conventional aggregometry and the VerifyNow P2Y12 assay. Genotyping was performed for CYP2C19*2/3, CYP3A53, and ABCB1 C3435T alleles. The primary endpoint was the absolute change in 20 μM ADP-induced MPA. After switching, MPAs after stimuli with 20 and 5 μM ADP were decreased by 6.6% (95% confidence interval: 3.2-10.1%; P < 0.001), and 6.3% (95% confidence interval: 2.5-10.2%; P = 0.002), respectively. Fifty-two P2Y12 reaction units fell (95% confidence interval: 35-70; P < 0.001) and the prevalence of HPR decreased (24%; P < 0.001). Pharmacodynamic effects were similar after rosuvastatin and pravastatin therapy. In addition to smoking status, the combination of calcium channel blocker usage and ABCB1 C3435T genotype significantly affected the change of 20 μM ADP-induced MPA.
Among PCI-treated patients with HPR during co-administration of clopidogrel and atorvastatin, switching to a non-CYP3A4-metabolized statin can significantly decrease platelet reactivity and the prevalence of HPR. This switching effect appears similar irrespective of the type of non-CYP3A4-metabolized statin.
CYP3A4 代谢的他汀类药物会影响氯吡格雷的药效动力学效应。我们旨在评估在服用阿托伐他汀和氯吡格雷且血小板反应高（HPR）的患者中，切换为非 CYP3A4 代谢的他汀类药物对血小板功能的影响。
在接受氯吡格雷（75mg/天）和阿托伐他汀（10mg/天）（≥6 个月）的慢性治疗期间，经皮冠状动脉介入治疗（PCI）治疗的患者（n=50），HPR[20μM 二磷酸腺苷（ADP）诱导的最大血小板聚集（MPA）>50%]入选。他们被随机分为接受为期 15 天的治疗，一组服用瑞舒伐他汀 10mg/天（n=25），另一组服用普伐他汀 20mg/天（n=25）。通过常规聚集测定和 VerifyNow P2Y12 测定在切换前后评估血小板功能。对 CYP2C19*2/3、CYP3A53 和 ABCB1 C3435T 等位基因进行基因分型。主要终点是 20μM ADP 诱导的 MPA 的绝对变化。转换后，20μM 和 5μM ADP 刺激的 MPA 分别降低 6.6%（95%置信区间：3.2-10.1%；P<0.001）和 6.3%（95%置信区间：2.5-10.2%；P=0.002）。52 个 P2Y12 反应单位下降（95%置信区间：35-70；P<0.001），HPR 发生率降低（24%；P<0.001）。瑞舒伐他汀和普伐他汀治疗后的药效学效应相似。除吸烟状况外，钙通道阻滞剂的使用和 ABCB1 C3435T 基因型的组合显著影响 20μM ADP 诱导的 MPA 的变化。
在服用氯吡格雷和阿托伐他汀且 HPR 的 PCI 治疗患者中，切换为非 CYP3A4 代谢的他汀类药物可显著降低血小板反应性和 HPR 的发生率。这种转换效果似乎与非 CYP3A4 代谢的他汀类药物的类型无关。
