临床实施快速 CYP2C19 基因分型指导经皮冠状动脉介入治疗后的抗血小板治疗。
Clinical implementation of rapid CYP2C19 genotyping to guide antiplatelet therapy after percutaneous coronary intervention.
机构信息
Department of Pharmacotherapy and Translational Research, University of Florida, Gainesville, FL, USA.
Center for Pharmacogenomics, University of Florida, Gainesville, FL, USA.
出版信息
J Transl Med. 2018 Apr 11;16(1):92. doi: 10.1186/s12967-018-1469-8.
BACKGROUND
The CYP2C19 nonfunctional genotype reduces clopidogrel effectiveness after percutaneous coronary intervention (PCI). Following clinical implementation of CYP2C19 genotyping at University Florida (UF) Health Shands Hospital in 2012, where genotype results are available approximately 3 days after PCI, testing was expanded to UF Health Jacksonville in 2016 utilizing a rapid genotyping approach. We describe metrics with this latter implementation.
METHODS
Patients at UF Health Jacksonville undergoing left heart catheterization with intent to undergo PCI were targeted for genotyping using the Spartan RX™ system. Testing metrics and provider acceptance of testing and response to genotype results were examined, as was antiplatelet therapy over the 6 months following genotyping.
RESULTS
In the first year, 931 patients, including 392/505 (78%) total patients undergoing PCI, were genotyped. The median genotype test turnaround time was 96 min. Genotype results were available for 388 (99%) PCI patients prior to discharge. Of 336 genotyped PCI patients alive at discharge and not enrolled in an antiplatelet therapy trial, 1/6 (17%) poor metabolizers (PMs, with two nonfunctional alleles), 38/93 (41%) intermediate metabolizers (IMs, with one nonfunctional allele), and 119/237 (50%) patients without a nonfunctional allele were prescribed clopidogrel (p = 0.110). Clopidogrel use was higher among non-ACS versus ACS patients (78.6% vs. 42.2%, p < 0.001). Six months later, among patients with follow-up data, clopidogrel was prescribed in 0/4 (0%) PMs, 33/65 (51%) IMs, and 115/182 (63%) patients without a nonfunctional allele (p = 0.008 across groups; p = 0.020 for PMs versus those without a nonfunctional allele).
CONCLUSION
These data demonstrate that rapid genotyping is clinically feasible at a high volume cardiac catheterization facility and allows informed chronic antiplatelet prescribing, with lower clopidogrel use in PMs at 6 months. Trial registration ClinicalTrials.gov Identifier: NCT02724319; registered March 31, 2016; https://www.clinicaltrials.gov/ct2/show/NCT02724319?term=angiolillo&rank=7.
背景
CYP2C19 非功能基因型会降低经皮冠状动脉介入治疗（PCI）后的氯吡格雷疗效。2012 年，佛罗里达大学健康山医院（UF Health Shands Hospital）开始实施 CYP2C19 基因分型，大约在 PCI 后 3 天即可获得基因型结果。2016 年，UF 健康杰克逊维尔医院（UF Health Jacksonville）利用快速基因分型方法扩展了该检测。我们描述了后一种实施方式的指标。
方法
UF 健康杰克逊维尔医院行左心导管术并计划行 PCI 的患者，使用 Spartan RX™系统进行基因分型。检查了检测指标以及提供者对检测的接受程度和对基因型结果的反应，同时还检查了基因分型后 6 个月内的抗血小板治疗情况。
结果
在第一年，931 名患者（包括 505 名 PCI 患者中的 392 名）进行了基因分型。中位基因型检测周转时间为 96 分钟。388 名（99%）接受 PCI 的患者在出院前获得了基因型结果。在 336 名接受基因分型的 PCI 存活出院且未参加抗血小板治疗试验的患者中，1/6（17%）为弱代谢者（PM，有两个无功能等位基因），38/93（41%）为中间代谢者（IM，有一个无功能等位基因），119/237（50%）患者无无功能等位基因，均接受氯吡格雷治疗（p=0.110）。非急性冠脉综合征（ACS）患者的氯吡格雷使用率高于 ACS 患者（78.6% vs. 42.2%，p<0.001）。6 个月后，在有随访数据的患者中，PM 患者中无一例（0%）、IM 患者中 33 例（51%）、无功能等位基因患者中 115 例（63%）服用氯吡格雷（各组间 p<0.001；PM 与无功能等位基因患者间 p=0.020）。
结论
这些数据表明，快速基因分型在高容量心脏导管室具有临床可行性，并允许进行知情的慢性抗血小板治疗，PM 患者在 6 个月时氯吡格雷的使用率更低。试验注册临床试验.gov 标识符：NCT02724319；注册于 2016 年 3 月 31 日；https://www.clinicaltrials.gov/ct2/show/NCT02724319?term=angiolillo&rank=7。
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