University of Maryland School of Medicine, Department of Medicine and Program for Personalized and Genomic Medicine, Baltimore, MD, USA.
University of Pittsburgh School of Pharmacy, Department of Pharmacy and Therapeutics, Pittsburgh, PA, USA.
Genet Med. 2020 Nov;22(11):1898-1902. doi: 10.1038/s41436-020-0894-2. Epub 2020 Jul 17.
Genotype-guided antiplatelet therapy is increasingly being incorporated into clinical care. The purpose of this study is to determine the extent to which patients initially genotyped for CYP2C19 to guide antiplatelet therapy were prescribed additional medications affected by CYP2C19.
We assembled a cohort of patients from eight sites performingCYP2C19 genotyping to inform antiplatelet therapy. Medication orders were evaluated from time of genotyping through one year. The primary endpoint was the proportion of patients prescribed two or more CYP2C19 substrates. Secondary endpoints were the proportion of patients with a drug-genotype interaction and time to receiving a CYP2C19 substrate.
Nine thousand one hundred ninety-one genotyped patients (17% nonwhite) with a mean age of 68 ± 3 years were evaluated; 4701 (51%) of patients received two or more CYP2C19 substrates and 3835 (42%) of patients had a drug-genotype interaction. The average time between genotyping and CYP2C19 substrate other than antiplatelet therapy was 25 ± 10 days.
More than half of patients genotyped in the setting of CYP2C19-guided antiplatelet therapy received another medication impacted by CYP2C19 in the following year. Given that genotype is stable for a patient's lifetime, this finding has implications for cost effectiveness, patient care, and treatment outcomes beyond the indication for which it was originally performed.
基因指导的抗血小板治疗越来越多地被纳入临床治疗。本研究旨在确定最初进行 CYP2C19 基因分型以指导抗血小板治疗的患者被开处受 CYP2C19 影响的其他药物的程度。
我们从进行 CYP2C19 基因分型以告知抗血小板治疗的 8 个地点组建了一个患者队列。从基因分型到一年期间评估药物医嘱。主要终点是规定两种或更多 CYP2C19 底物的患者比例。次要终点是具有药物-基因型相互作用的患者比例和接受 CYP2C19 底物的时间。
评估了 9191 名经基因分型的患者(17%为非白人),平均年龄为 68±3 岁;4701 名(51%)患者接受两种或更多 CYP2C19 底物,3835 名(42%)患者存在药物-基因型相互作用。基因分型和除抗血小板治疗以外的 CYP2C19 底物之间的平均时间为 25±10 天。
在 CYP2C19 指导的抗血小板治疗背景下进行基因分型的患者中,超过一半的患者在接下来的一年中接受了另一种受 CYP2C19 影响的药物。鉴于基因型对患者的终生稳定,这一发现对成本效益、患者护理和治疗结果具有重要意义,超出了最初进行基因分型的适应证。