Department of Pharmacotherapy and Translational Research, University of Florida, Gainesville, Florida.
Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy and McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
JACC Cardiovasc Interv. 2018 Jan 22;11(2):181-191. doi: 10.1016/j.jcin.2017.07.022. Epub 2017 Nov 1.
This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI).
CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI.
After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights.
Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60).
These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.
本多中心实用研究评估了经皮冠状动脉介入治疗（PCI）后 CYP2C19 基因指导的抗血小板治疗临床实施后的结局。
CYP2C19 失活等位基因可削弱 PCI 后氯吡格雷的疗效。
临床基因分型后，各机构建议 PCI 患者携带失活等位基因时采用替代抗血小板治疗（普拉格雷、替格瑞洛）。比较 PCI 后 12 个月内携带失活等位基因的患者接受氯吡格雷与替代治疗的主要不良心血管事件（定义为心肌梗死、卒中和死亡）。还比较了无失活等位基因和携带失活等位基因的患者接受替代治疗的风险。采用 Cox 回归，通过逆概率治疗权重调整组间差异。
在 1815 例患者中，572 例（31.5%）携带失活等位基因。携带失活等位基因的患者接受氯吡格雷治疗与替代治疗相比，主要不良心血管事件的风险显著更高（23.4 与 8.7 例/100 患者年；调整后的危险比：2.26；95%置信区间：1.18 至 4.32；p=0.013）。在 PCI 时患有急性冠脉综合征的 1210 例患者中也观察到类似结果（调整后的危险比：2.87；95%置信区间：1.35 至 6.09；p=0.013）。无失活等位基因的患者与携带失活等位基因的患者接受替代治疗的主要不良心血管事件无差异（调整后的危险比：1.14；95%置信区间：0.69 至 1.88；p=0.60）。
这些来自真实世界观察的数据表明，如果患者接受氯吡格雷而非替代治疗，CYP2C19 失活等位基因与更高的心血管事件风险相关。未来的基因型指导抗血小板治疗随机研究可能具有价值。
