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使用羟氯喹及伴发致心律失常药物导致的QTc间期延长:一项利用电子健康记录数据的回顾性研究

QTc Prolongation with the Use of Hydroxychloroquine and Concomitant Arrhythmogenic Medications: A Retrospective Study Using Electronic Health Records Data.

作者信息

Villa Zapata Lorenzo, Boyce Richard D, Chou Eric, Hansten Philip D, Horn John R, Gephart Sheila M, Subbian Vignesh, Romero Andrew, Malone Daniel C

机构信息

Department of Pharmacy Practice, College of Pharmacy, Mercer University, Atlanta, GA, USA.

Department of Biomedical Informatics, School of Medicine, University of Pittsburgh, The Offices@Baum, 5607 Baum Blvd, Pittsburgh, PA, 15202, USA.

出版信息

Drugs Real World Outcomes. 2022 Sep;9(3):415-423. doi: 10.1007/s40801-022-00307-5. Epub 2022 Jun 5.

Abstract

INTRODUCTION

Hydroxychloroquine can induce QT/QTc interval prolongation for some patients; however, little is known about its interactions with other QT-prolonging drugs.

OBJECTIVE

The purpose of this retrospective electronic health records study was to evaluate changes in the QTc interval in patients taking hydroxychloroquine with or without concomitant QT-prolonging medications.

METHODS

De-identified health records were obtained from the Cerner Health Facts database. Variables of interest included demographics, diagnoses, clinical procedures, laboratory tests, and medications. Patients were categorized into six cohorts based on exposure to hydroxychloroquine, methotrexate, or sulfasalazine alone, or the combination of any those drugs with any concomitant drug known to prolong the QT interval. Tisdale QTc risk score was calculated for each patient cohort. Two-sample paired t-tests were used to test differences between the mean before and after QTc measurements within each group and ANOVA was used to test for significant differences across the cohort means.

RESULTS

A statistically significant increase in QTc interval from the last measurement prior to concomitant exposure of 18.0 ms (95% CI 3.5-32.5; p < 0.05) was found in the hydroxychloroquine monotherapy cohort. QTc changes varied considerably across cohorts, with standard deviations ranging from 40.9 (hydroxychloroquine monotherapy) to 57.8 (hydroxychloroquine + sulfasalazine). There was no difference in QTc measurements among cohorts. The hydroxychloroquine + QTc-prolonging agent cohort had the highest average Tisdale Risk Score compared with those without concomitant exposure (p < 0.05).

CONCLUSION

Our analysis of retrospective electronic health records found hydroxychloroquine to be associated with a moderate increase in the QTc interval compared with sulfasalazine or methotrexate. However, the QTc was not significantly increased with concomitant exposure to other drugs known to increase QTc interval.

摘要

引言

羟氯喹可能会使部分患者的QT/QTc间期延长;然而,对于其与其他可延长QT间期的药物之间的相互作用,人们了解甚少。

目的

这项回顾性电子健康记录研究的目的是评估服用羟氯喹的患者在联合或不联合使用可延长QT间期的药物时QTc间期的变化。

方法

从Cerner健康事实数据库获取去识别化的健康记录。感兴趣的变量包括人口统计学信息、诊断结果、临床操作、实验室检查和用药情况。根据患者单独使用羟氯喹、甲氨蝶呤或柳氮磺胺吡啶,或这些药物中的任何一种与已知可延长QT间期的任何伴随药物联合使用的情况,将患者分为六个队列。计算每个患者队列的蒂斯代尔QTc风险评分。使用两样本配对t检验来检验每组内QTc测量前后平均值之间的差异,并使用方差分析来检验各队列平均值之间的显著差异。

结果

在羟氯喹单药治疗队列中,发现QTc间期较联合用药前的最后一次测量值有统计学意义的增加,增加了18.0毫秒(95%置信区间3.5 - 32.5;p < 0.05)。各队列间QTc变化差异很大,标准差范围从40.9(羟氯喹单药治疗)到57.8(羟氯喹 + 柳氮磺胺吡啶)。各队列间QTc测量值无差异。与未联合用药的队列相比,羟氯喹 + 可延长QT间期药物队列的平均蒂斯代尔风险评分最高(p < 0.05)。

结论

我们对回顾性电子健康记录的分析发现,与柳氮磺胺吡啶或甲氨蝶呤相比,羟氯喹与QTc间期适度增加有关。然而,联合使用其他已知可增加QTc间期的药物时,QTc并未显著增加。

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