Association Between Melatonin Receptor Agonists and Cardiac Arrhythmia; Disproportionality Analysis Studies Using Pharmacovigilance Databases

Abstract

Among the drugs used for insomnia, the use of benzodiazepine and non-benzodiazepine hypnotics is correlated to the occurrence of cardiac arrhythmia. Conversely, melatonin receptor agonists may exert cardioprotective effects. Therefore, in the present study, we investigated the association between the use of melatonin receptor agonists and the occurrence of cardiac arrhythmia using the Food and Drug Administration Adverse Event Reporting System (FAERS). Eligible patients are registered in FAERS. The targeted drugs were melatonin receptor agonists and benzodiazepine receptor agonists (BZRAs). The target disease was cardiac arrhythmia, and data for the disease were extracted from the Medical Dictionary for Regulatory Activities (MedDRA) 27.1; Standardized MedDRA Query (SMQ). The reporting odds ratio (ROR) was calculated in the study. The results showed that melatonin receptor agonists were negatively correlated with all cardiac arrhythmia-related SMQs. The RORs for each SMQ were as follows: "cardiac arrhythmias" (ROR: 0.47, 95%CI: 0.41-0.54), "bradyarrhythmias" (ROR: 0.20, 95%CI: 0.10-0.40), "tachyarrhythmias" (ROR: 0.21, 95%CI: 0.13-0.33), "supraventricular tachyarrhythmias" (ROR: 0.24, 95%CI: 0.14-0.41), "ventricular tachyarrhythmias" (ROR: 0.05, 95%CI: 0.01-0.33), and "TdP" (ROR: 0.32, 95%CI: 0.25-0.41). Conversely, BZRAs were positively correlated with cardiac arrhythmia-related SMQs. Overall, the present results suggest that compared with BZRAs, melatonin receptor agonist usage is weakly associated with cardiac arrhythmia.

Keywords: Cardiac arrhythmia; Disproportionality analysis; FDA Adverse Event Reporting System; Melatonin receptor agonists; Pharmacovigilance.