Pharmacy Department, Marshfield Clinic Health Systems, Marshfield, WI.
Center for Human Genetics, Marshfield Clinic Research Institute, Marshfield, WI.
Am J Health Syst Pharm. 2019 Feb 21;76(6):387-397. doi: 10.1093/ajhp/zxy072.
As a preliminary evaluation of the outcomes of implementing pharmacogenetic testing within a large rural healthcare system, patients who received pre-emptive pharmacogenetic testing and warfarin dosing were monitored until June 2017.
Over a 20-month period, 749 patients were genotyped for VKORC1 and CYP2C9 as part of the electronic Medical Records and Genomics Pharmacogenetics (eMERGE PGx) study. Of these, 27 were prescribed warfarin and received an alert for pharmacogenetic testing pertinent to warfarin; 20 patients achieved their target international normalized ratio (INR) of 2.0-3.0, and 65% of these patients achieved target dosing within the recommended pharmacogenetic alert dose (± 0.5 mg/day). Of these, 10 patients had never been on warfarin prior to the alert and were further evaluated with regard to time to first stable target INR, bleeds and thromboembolic events, hospitalizations, and mortality. There was a general trend of faster time to first stable target INR when the patient was initiated at a warfarin dose within the alert recommendation versus a dose outside of the alert recommendation with a mean (± SD) of 34 (± 28) days versus 129 (± 117) days, respectively. No trends regarding bleeds, thromboembolic events, hospitalization, or mortality were identified with respect to the pharmacogenetic alert. The pharmacogenetic alert provided pharmacogenetic dosing information to prescribing clinicians and appeared to deploy appropriately with the correct recommendation based upon patient genotype.
Implementing pharmacogenetic testing as a standard of care service in anticoagulation monitoring programs may improve dosage regimens for patients on anticoagulation therapy.
作为在大型农村医疗体系中实施药物遗传学检测结果的初步评估，对接受预防性药物遗传学检测和华法林剂量调整的患者进行监测，直至 2017 年 6 月。
在 20 个月的时间里，有 749 名患者接受了 VKORC1 和 CYP2C9 的基因分型，作为电子病历和基因组药物遗传学（eMERGE PGx）研究的一部分。其中，27 名患者被开处华法林，并收到了与华法林相关的药物遗传学检测警报；20 名患者达到了国际标准化比值（INR）目标值 2.0-3.0，其中 65%的患者达到了推荐的药物遗传学警报剂量（±0.5mg/天）范围内的目标剂量。其中，10 名患者在警报前从未服用过华法林，进一步评估了首次稳定目标 INR 的时间、出血和血栓栓塞事件、住院和死亡率。与剂量超出警报建议范围的患者相比，当患者的起始华法林剂量在警报建议范围内时，首次稳定目标 INR 的时间有更快的趋势，平均（±SD）分别为 34（±28）天和 129（±117）天。在药物遗传学警报方面，未发现出血、血栓栓塞事件、住院或死亡率的趋势。药物遗传学警报为处方医生提供了药物遗传学剂量信息，并根据患者的基因型进行了适当的部署，提出了正确的建议。
将药物遗传学检测作为抗凝监测项目的标准护理服务实施，可能会改善接受抗凝治疗患者的剂量方案。
