# Cardiac disorders associated with compound long-acting bronchodilators for inhalation: a pharmacovigilance analysis of the FDA adverse event reporting system database

## TL;DR

This study analyzed FDA data to find that compound inhaled bronchodilators are linked to significant heart-related side effects, especially in the early stages of treatment.

## Contribution

The study provides new insights into the cardiovascular risks of compound long-acting bronchodilators using FAERS data.

## Key findings

- Atrial fibrillation, myocardial infarction, and heart failure were the most common cardiac adverse events.
- Triple inhaled formulations showed higher rates of specific adverse events compared to dual bronchodilators.
- Most cardiac adverse events occurred within 90 days of treatment initiation.

## Abstract

This study aimed to utilize the FDA Adverse Event Reporting System (FAERS) database to systematically investigate the relationship between compound inhaled long-acting bronchodilators for inhalation (ILABs) and cardiovascular adverse events.

We conducted a pharmacovigilance analysis using cardiac adverse event (CAE) reports submitted to FAERS between January 2014 and September 30, 2024. We compared the cardiac toxicity signal intensity of various compound ILABs using the proportional imbalance measurement method. Additionally, we performed subgroup analyses considering factors such as composition, onset time, mortality outcome case information, and concomitant adverse events.

Our study comprised 3,120 reports on the use of compound ILABs, involving 653 CAEs (454 reports). The most prevalent CAEs observed were atrial fibrillation (14.93%), myocardial infarction (14.37%), cardiac failure congestive (10.96%), cardiac disorder (8.70%), and cardiogenic shock (8.13%). Approximately 20% of CAEs occurred on day 0, and roughly 50% occurred within 90 days. The proportion of CAE reports was similar for triple inhalation formulations and double bronchodilators. But the number of adverse events such as congestive cardiac failure, coronary artery disease, and ventricular extrasystoles associated with triple inhaled formulations was significantly higher than that with dual bronchodilators, with no such reports for the latter. 84.58% of CAE cases were linked to other adverse events.

Compound ILABs had significant CAE risk signals, especially those of atrial fibrillation, myocardial infarction and heart failure, and the risk signal was stronger in the early stage of drug treatment. Except for a few individual adverse events, the overall CAE risk signal associated with triple inhaled agents (mainly Fluticasone/umeclidinium/vilanterol) was comparable to that of dual bronchodilators.