Cardiac disorder-related adverse events for aryl hydrocarbon receptor agonists: a safety review

Area of Science:

• Pharmacovigilance
• Cardiovascular Safety
• Drug Metabolism

Background:

• Cardiac disorder-related adverse events (AEs) have been reported with aryl hydrocarbon receptor (AHR) agonists.
• The comprehensive safety profiles of AHR agonists concerning cardiac health remain largely unknown.
• This study aimed to identify and evaluate significant cardiac disorders associated with AHR agonists.

Purpose of the Study:

• To investigate the association between AHR agonist usage and cardiac disorder-related adverse events.
• To evaluate the safety profile of AHR agonists regarding cardiovascular health.
• To identify specific cardiac disorders and AHR agonists with potential safety signals.

Main Methods:

• Utilized OpenVigil 2.1 and the Food and Drug Administration Adverse Event Reporting System (FAERS) database (2004-2020).
• Employed Medical Dictionary for Regulatory Activities (MedDRA) and standardized MedDRA Queries for term definition.
• Applied the reporting odds ratio (ROR) method to detect adverse event signals.

Main Results:

• Identified 14,078 cardiac disorder-related AEs in patients receiving AHR agonists.
• Detected 93 preferred terms (PTs) with positive safety signals for cardiac disorders among AHR agonists.
• Peripheral swelling (1572 cases) and atrial fibrillation (1277 cases) were the most frequently reported cardiac AEs.
• Several AHR agonists showed a strong association with tachyarrhythmia.

Conclusions:

• Mining the FAERS database provided valuable insights into the cardiac safety of AHR agonists.
• The findings highlight specific cardiac risks, such as peripheral swelling and atrial fibrillation, associated with AHR agonist use.
• Further investigation into the cardiovascular safety of AHR agonists is warranted.