Disproportionality Analysis of Ivabradine in the US FDA Adverse Event Reporting System: A Real-World Study Across Overall and Indication-Specific Populations

Abstract

Background: Ivabradine, a selective I_f current inhibitor, is widely prescribed for heart failure and chronic angina; however, its post-marketing safety profile across diverse clinical contexts remains underexplored.

Objective: This study analyzed ivabradine-associated adverse events (AEs) using the US Food and Drug Administration Adverse Event Reporting System, with a focus on overall patterns and indication-specific subgroups.

Methods: We reviewed reports from the US Food and Drug Administration Adverse Event Reporting System from quarter 2, 2015, to quarter 2, 2024, and conducted a disproportionality analysis using four methods: reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and empirical Bayesian geometric mean. We stratified AEs by clinical indications (tachycardia, heart failure, coronary artery disease) and prioritized them using a semi-quantitative scoring system and important or designated medical event criteria as defined by the European Medicines Agency.

Results: A total of 2733 ivabradine-related AE reports were identified, involving 24 system organ classes. Cardiac disorders (n = 1045) and eye disorders (n = 352) were most frequent, with bradycardia, arrhythmias, and photopsia being the leading events. Subgroup analyses revealed distinct AE profiles: sinus tachycardia and supraventricular tachycardia in the tachycardia subgroup; blurred vision and angina in coronary artery disease; and severe AEs-such as dyspnea, prolonged QT interval, and ventricular fibrillation-primarily in heart failure. One rare but notable designated medical event, transient blindness (n = 3), was also identified.

Conclusion: Ivabradine shows an overall favorable safety profile. Most AEs appear related to underlying disease or comedications rather than intrinsic drug toxicity. These findings support indication-specific monitoring to enhance clinical safety and pharmacovigilance.