Impact of CYP2C19 Genetic Testing on Provider Prescribing Patterns for Antiplatelet Therapy After Acute Coronary Syndromes and Percutaneous Coronary Intervention
Impact of CYP2C19 Genetic Testing on Provider Prescribing Patterns for Antiplatelet Therapy After Acute Coronary Syndromes and Percutaneous Coronary Intervention
复制标题
DOI：
10.1161/circoutcomes.113.000321
复制
发表时间：
2013-11-01
影响因子：
6.9
通讯作者：
Choudhry, Niteesh K.
中科院分区：
文献类型：
--
作者：
Desai, Nihar R.;Canestaro, William J.;Choudhry, Niteesh K.
背景-接受氯吡格雷治疗的患者如果有>= 1个CYP 2C 19功能缺失等位基因，则发生不良心血管事件的风险增加。2010年，美国食品和药物管理局发布了一个黑框警告，警告不要在此类患者中使用氯吡格雷。我们试图评估CYP 2C 19基因检测对急性冠状动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。方法和结果：最近急性冠状动脉综合征或经皮冠状动脉介入治疗患者接受了CYP 2C 19检测。基因型和表型结果提供给患者和他们的医生，但没有提出具体的治疗建议。患者根据其基因型（携带者与非携带者）和表型（广泛，中间和弱代谢者）进行分类。主要结局是抗血小板治疗的强化，定义为氯吡格雷剂量递增或用普拉格雷替代氯吡格雷。在2010年7月至2012年4月期间，确定了6032例患者，其中499例（8.3%）进行了CYP 2C 19基因分型，发现其中146例（30%）具有>= 1个功能降低等位基因，包括15例（3%）具有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加强抗血小板治疗，但只有20%的氯吡格雷弱代谢者加强了抗血小板治疗。但只有20%的氯吡格雷弱代谢者增加了氯吡格雷的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和证据不断发展。
Background-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.Methods and Results-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.Conclusions-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.