心脏手术中术后心房颤动的抢先药物遗传学指导美托洛尔管理：心脏手术中房颤的抢先药物遗传学指导美托洛尔管理先导试验。

Preemptive Pharmacogenetic-Guided Metoprolol Management for Postoperative Atrial Fibrillation in Cardiac Surgery: The Preemptive Pharmacogenetic-Guided Metoprolol Management for Atrial Fibrillation in Cardiac Surgery Pilot Trial.

机构信息

Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN.

Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN.

出版信息

J Cardiothorac Vasc Anesth. 2023 Oct;37(10):1974-1982. doi: 10.1053/j.jvca.2023.06.017. Epub 2023 Jun 14.

DOI:10.1053/j.jvca.2023.06.017

PMID:37407326

Abstract

OBJECTIVES

To test the hypothesis that implementation of a cytochrome P-450 2D6 (CYP2D6) genotype-guided perioperative metoprolol administration will reduce the risk of postoperative atrial fibrillation (AF), the authors conducted the Preemptive Pharmacogenetic-Guided Metoprolol Management for Atrial Fibrillation in Cardiac Surgery pilot study.

DESIGN

Clinical pilot trial.

SETTING

Single academic center.

PARTICIPANTS

Seventy-three cardiac surgery patients.

MEASUREMENTS AND MAIN RESULTS

Patients were classified as normal, intermediate, poor, or ultrarapid metabolizers after testing for their CYP2D6 genotype. A clinical decision support tool in the electronic health record advised providers on CYP2D6 genotype-guided metoprolol dosing. Using historical data, the Bayesian method was used to compare the incidence of postoperative AF in patients with altered metabolizer status to the reference incidence. A logistic regression analysis was performed to study the association between the metabolizer status and postoperative AF while controlling for the Multicenter Study of Perioperative Ischemia AF Risk Index. Of the 73 patients, 30% (n = 22) developed postoperative AF; 89% (n = 65) were normal metabolizers; 11% (n = 8) were poor/intermediate metabolizers; and there were no ultrarapid metabolizer patients identified. The estimated rate of postoperative AF in patients with altered metabolizer status was 30% (95% CI 8%-60%), compared with the historical reference incidence (27%). In the risk-adjusted analysis, there was insufficient evidence to conclude that modifying metoprolol dosing based on poor/intermediate metabolizer status was associated significantly with the odds of postoperative AF (odds ratio 0.82, 95% CI 0.15-4.55, p = 0.82).

CONCLUSIONS

A CYP2D6 genotype-guided metoprolol management was not associated with a reduction of postoperative AF after cardiac surgery.

摘要

目的

检验假设，即实施细胞色素 P-450 2D6（CYP2D6）基因指导的围手术期美托洛尔给药将降低术后心房颤动（AF）的风险，作者进行了心脏手术中抢先进行的药物遗传学指导美托洛尔管理预防心房颤动的先导性研究。

设计

临床先导试验。

设置

单一学术中心。

参与者

73 例心脏手术患者。

测量和主要结果

在对 CYP2D6 基因型进行检测后，患者被分类为正常、中间、差或超快代谢者。电子病历中的临床决策支持工具为 CYP2D6 基因指导的美托洛尔剂量提供建议。使用历史数据，贝叶斯方法用于比较代谢改变患者术后 AF 的发生率与参考发生率。进行逻辑回归分析以研究代谢状态与术后 AF 之间的关联，同时控制多中心围手术期缺血性 AF 风险指数。在 73 例患者中，30%（n=22）发生术后 AF；89%（n=65）为正常代谢者；11%（n=8）为差/中间代谢者；未发现超快代谢者。改变代谢者状态的患者术后 AF 的估计发生率为 30%（95%CI 8%-60%），而历史参考发生率为 27%。在风险调整分析中，没有足够的证据表明根据差/中间代谢者状态调整美托洛尔剂量与术后 AF 的几率显著相关（比值比 0.82，95%CI 0.15-4.55，p=0.82）。