Proarrhythmia associated with antiarrhythmic drugs: a comprehensive disproportionality analysis of the FDA adverse event reporting system

Abstract

Objective: This study aimed to identify the different associations between antiarrhythmic drugs (AADs) and arrhythmias, and to determine whether pharmacokinetic drug interactions involving AADs increase the risk of AAD-related arrhythmias compared to using AADs alone.Materials and methods: The disproportionality analysis of AAD-associated cardiac arrhythmias, including AAD monotherapies and concomitant use of pharmacokinetic interacting agents involving AADs, was conducted by using reporting odds ratio (ROR) and information component (IC) as detection of potential safety signals based on FAERS data from January 2016 to June 2022. We compared the clinical features of patients reported with AAD–associated arrhythmias between fatal and non-fatal groups, and further investigated the onset time (TTO) following different AAD regimens.Results: A total of 11754 AAD–associated cardiac arrhythmias reports were identified, which was more likely to occur in the elderly (52.17%). Significant signals were detected between cardiac arrhythmia and all AAD monotherapies, with ROR ranging from 4.86 with mexiletine to 11.07 with flecainide. Regarding four specific arrhythmias in High Level Term (HLT) level, the AAD monotherapies with the highest ROR were flecainide in cardiac conduction disorders (ROR025 = 21.18), propafenone in rate and rhythm disorders (ROR025 = 10.36), dofetilide in supraventricular arrhythmias (ROR025 = 17.61), and ibutilide in ventricular arrhythmias (ROR025 = 4.91). Dofetilide/ibutilide, ibutilide, mexiletine/ibutilide and dronedarone presented no signal in the above four specific arrhythmias respectively. Compared with amiodarone monotherapy, sofosbuvir plus amiodarone detected the most significantly increased ROR in arrhythmias.Conclusion: The investigation showed the spectrum and risk of AAD–associated cardiac arrhythmias varied among different AAD therapies. The early identification and management of AAD-associated arrhythmias are of great importance in clinical practice.

Tic-Tac: A Translational Approach in Mechanisms Associated with Irregular Heartbeat and Sinus Rhythm Restoration in Atrial Fibrillation Patients

“…Clinical guidelines recommend the use of a limited number of AAD for the clinical management of patients [ 1 ], despite the existence of a wide range of these medications [ 88 ], including some that can limit the occurrence of proarrhythmic events, which constitutes the main limitation of the classical drugs used in AF [ 89 ]. This is reflected in the use of class I antiarrhythmics such as propafenone and flecainide, and class III antiarrhythmics such as amiodarone, despite the development of several antiarrhythmics over the years [ 90 ].…”

Assessing the safety of bedaquiline: insight from adverse event reporting system analysis

“…AE information in the FAERS database is documented and analyzed individually, making the data more basic ( Wang J. et al, 2023 ). By mining AE signals in FAERS, unrecognized safety signals can be managed during clinical development for risk management purposes ( Wang F. et al, 2023 ). Network pharmacology is a discipline that utilizes systems biology and computer technology to construct networks and investigate the interactions between “disease-gene-target-drug” ( Lin et al, 2022 ; Liu et al, 2023 ).…”