Introduction:

Drug-induced QT_c-prolongation is a well-known adverse drug reaction (ADR), however there is limited knowledge of other drug-induced arrhythmias.

Purpose:

The objective of this study is to determine the drugs reported to be associated with arrhythmias other than QT_c-prolongation using the FAERS database, possibly identifying potential drug causes that have not been reported previously.

Methods:

FAERS reports from 2004 quarter 1 through 2019 quarter 1 were combined to create a dataset of approximately 11.6 million reports. Search terms for arrhythmias of interest were selected from the Standardized MedDRA Queries (SMQ) Version 12.0. Frequency of the cardiac arrhythmias were determined for atrial fibrillation, atrioventricular block, bradyarrhythmia, bundle branch block, supraventricular tachycardia, and ventricular fibrillation and linked to the reported causal medications. Reports were further categorized by prior evidence associations using package inserts and established drug databases. A reporting odds ratio (ROR) and confidence interval (CI) were calculated for the ADRs for each drug and each of the 6 cardiac arrhythmias.

Results:

Of the 11.6 million reports in the FAERS database, 68,989 were specific to cardiac arrhythmias of interest. There were 61 identified medication-reported arrhythmia pairs for the 6 arrhythmia groups with 33 found to have an unknown reported association. Rosiglitazone was the most frequently medication reported across all arrhythmias [ROR 6.02 (CI: 5.82-6.22)]. Other medications with significant findings included: rofecoxib, digoxin, alendronate, lenalidomide, dronedarone, zoledronic acid, adalimumab, dabigatran, and interferon beta-1b.

Conclusion:

Upon retrospective analysis of the FAERS database, the majority of drug-associated arrhythmias reported were unknown suggesting new potential drug causes. Cardiac arrhythmias other than QTc prolongation are a new area of focus for pharmacovigilance and medication safety. Consideration of future studies should be given to using the FAERS database as a timely pharmacovigilance tool to identify unknown adverse events of medications.

中文翻译：

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使用食品和药物管理局不良事件报告系统 (FAERS) 数据库，使用不成比例分析来识别以前未知的与药物相关的心律失常原因

介绍：

药物引起的 QT _c -延长是众所周知的药物不良反应 (ADR)，但对其他药物引起的心律失常知之甚少。

目的：

本研究的目的是使用 FAERS 数据库确定报告与 QT _{c -延长以外的心律失常相关的药物，可能确定以前未报告的潜在药物原因。}

方法：

从 2004 年第 1 季度到 2019 年第 1 季度的 FAERS 报告相结合，创建了一个包含约 1160 万份报告的数据集。从标准化 MedDRA 查询 (SMQ) 版本 12.0 中选择感兴趣的心律失常的搜索词。确定心房颤动、房室传导阻滞、心动过缓、束支传导阻滞、室上性心动过速和心室颤动的心律失常频率，并与报告的病因药物相关。使用包装插页和已建立的药物数据库，根据先前的证据关联对报告进行进一步分类。计算每种药物和 6 种心律失常中每种药物的 ADR 的报告优势比 (ROR) 和置信区间 (CI)。

结果：

在 FAERS 数据库中的 1160 万份报告中，有 68,989 份是针对感兴趣的心律失常的。对于 6 个心律失常组，有 61 对已确定的药物报告心律失常对，其中 33 个发现有未知的报告关联。罗格列酮是所有心律失常报告中最常见的药物 [ROR 6.02 (CI: 5.82-6.22)]。其他有显着发现的药物包括：罗非昔布、地高辛、阿仑膦酸盐、来那度胺、决奈达隆、唑来膦酸、阿达木单抗、达比加群和干扰素 beta-1b。

结论：

在对 FAERS 数据库进行回顾性分析后，报告的大多数与药物相关的心律失常是未知的，表明存在新的潜在药物原因。QTc 延长以外的心律失常是药物警戒和用药安全的一个新关注领域。未来的研究应考虑使用 FAERS 数据库作为及时的药物警戒工具来识别未知的药物不良事件。