A Real-World Disproportionality Analysis of Drug-Induced Heart Failure: Integrating FAERS Database and AHA Statement

Clinical Snapshot

Key Findings

• P Value: Not reported

• Effect Size: Not specified in abstract

• Primary Outcome: Drug-induced heart failure adverse event signals

• Nnt Or Sensitivity: Signal strength validation against AHA Class A drugs confirmed

• Confidence Interval: Not reported

Clinical Application

Results can inform prescribing decisions and monitoring protocols in routine practice Relevant to Australian practice as many identified drugs (rosiglitazone, pioglitazone, saxagliptin) are PBS-listed; findings support TGA pharmacovigilance and align with RACGP diabetes management guidelines emphasizing cardiovascular safety Patients prescribed identified high-risk medications, particularly diabetes and pulmonary hypertension drugs

Abstract

Heart failure (HF), the advanced stage of diverse cardiac conditions, poses a significant public health challenge. This study analyzes adverse event (AE) signals associated with HF within the FDA Adverse Event Reporting System (FAERS) database, offering critical insights to guide rational medication use in clinical settings. Adverse event reports (AERs) associated with HF in the FAERS database, spanning from the first quarter of 2004 to the fourth quarter of 2024, were analyzed. The potential HF risk of drugs was assessed using the disproportionality analysis, with findings juxtaposed against the American Heart Association (AHA) drug list. Drug-induced HF cases showed equivalent distribution between male and female, and high rates of rehospitalization and mortality. Prominent hypoglycemic drugs associated with HF included rosiglitazone, pioglitazone, and saxagliptin. Combination therapies, such as metformin/saxagliptin and metformin/rosiglitazone, also demonstrated elevated risks. In the context of pulmonary hypertension, drugs like macitentan, selexipag, and epoprostenol were particularly notable. Analysis against the AHA drug list confirmed stronger signal strength and frequency among Class A drugs, validating our results. Furthermore, drugs not flagged as positively signaling in the AHA registry, such as amiodarone, aliskiren, and testosterone, merit closer scrutiny due to their potential for adverse reactions. Our analysis of the FAERS database has identified medications associated with potential HF risks, providing valuable evidence to inform clinical decision-making and promote the safe use of medications.

References

1. 1.Li, D., Dong, Y., Yao, L., Chen, X., Li, Y., Deng, X., Li, J., Wang, M., & Fu, D. (2026). A real-world disproportionality analysis of drug-induced heart failure: Integrating FAERS database and AHA statement. Cardiovascular Toxicology. https://doi.org/10.1111/jdv.19703