Desai Nihar R, Canestaro William J, Kyrychenko Pavlo, Chaplin Donald, Martell Lori A, Brennan Troyen, Matlin Olga S, Choudhry Niteesh K
Section of Cardiovascular Medicine, Department of Medicine, Yale School of Medicine, and Center for Outcomes Research and Evaluation, Yale New Haven Health System, New Haven, CT.
Circ Cardiovasc Qual Outcomes. 2013 Nov;6(6):694-9. doi: 10.1161/CIRCOUTCOMES.113.000321. Epub 2013 Nov 5.
Patients treated with clopidogrel who have ≥1 loss of function alleles for CYP2C19 have an increased risk for adverse cardiovascular events. In 2010, the US Food and Drug Administration issued a boxed warning cautioning against the use of clopidogrel in such patients. We sought to assess the impact of CYP2C19 genetic testing on prescribing patterns for antiplatelet therapy among patients with acute coronary syndrome or percutaneous coronary intervention.
Patients with recent acute coronary syndrome or percutaneous coronary intervention prescribed clopidogrel were offered CYP2C19 testing. Genotype and phenotype results were provided to patients and their physicians, but no specific treatment recommendations were suggested. Patients were categorized based on their genotype (carriers versus noncarriers) and phenotype (extensive, intermediate, and poor metabolizers). The primary outcome was intensification in antiplatelet therapy defined as either dose escalation of clopidogrel or replacement of clopidogrel with prasugrel. Between July 2010 and April 2012, 6032 patients were identified, and 499 (8.3%) underwent CYP2C19 genotyping, of whom 146 (30%) were found to have ≥1 reduced function allele, including 15 (3%) with 2 reduced function alleles. Although reduced function allele carriers were significantly more likely than noncarriers to have an intensification of their antiplatelet therapy, only 20% of poor metabolizers of clopidogrel had their antiplatelet therapy intensified.
Providers were significantly more likely to intensify antiplatelet therapy in CYP2C19 allele carriers, but only 20% of poor metabolizers of clopidogrel had an escalation in the dose of clopidogrel or were switched to prasugrel. These prescribing patterns likely reflect the unclear impact and evolving evidence for clopidogrel pharmacogenomics.
接受氯吡格雷治疗且细胞色素P450 2C19（CYP2C19）功能缺失等位基因≥1个的患者发生不良心血管事件的风险增加。2010年，美国食品药品监督管理局发布了一项黑框警告，警示此类患者不要使用氯吡格雷。我们试图评估CYP2C19基因检测对急性冠脉综合征或经皮冠状动脉介入治疗患者抗血小板治疗处方模式的影响。
为近期发生急性冠脉综合征或接受经皮冠状动脉介入治疗且处方使用氯吡格雷的患者提供CYP2C19检测。将基因分型和表型结果告知患者及其医生，但未给出具体的治疗建议。根据患者的基因型（携带者与非携带者）和表型（快代谢型、中间代谢型和慢代谢型）进行分类。主要结局为抗血小板治疗强化，定义为氯吡格雷剂量增加或用普拉格雷替代氯吡格雷。在2010年7月至2012年4月期间，共识别出6032例患者，其中499例（8.3%）接受了CYP2C19基因分型，其中146例（30%）被发现有≥1个功能降低等位基因，包括15例（3%）有2个功能降低等位基因。虽然功能降低等位基因携带者比非携带者更有可能强化抗血小板治疗，但氯吡格雷慢代谢型患者中只有20%强化了抗血小板治疗。
医疗服务提供者在CYP2C19等位基因携带者中强化抗血小板治疗的可能性显著更高，但氯吡格雷慢代谢型患者中只有20%增加了氯吡格雷剂量或改用普拉格雷。这些处方模式可能反映了氯吡格雷药物基因组学的影响尚不明确且证据不断演变。
