A retrospective study of disproportionality analysis signals between proprotein convertase subtilisin/kexin 9 inhibitor use and respiratory, thoracic, and mediastinal disorders

This study aims to investigate emerging signals and clinical characteristics associated with adverse event reports of respiratory, thoracic, and mediastinal diseases (RTMD) related to proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) in the FDA Adverse Event Reporting System (FAERS) database. PCSK9i-related RTMD adverse event reports were extracted from the FAERS database (covering the period from the first quarter of 2016 to the fourth quarter of 2023), and the clinical characteristics and onset times of these reports were analyzed. The reporting odds ratio (ROR) and the Bayesian Confidence Propagation Neural Network (BCPNN) were used to calculate disproportionate signals in the adverse event reports. A total of 17,063 PCSK9i-related RTMD adverse event reports were extracted from the FAERS database. A summary of these reports revealed that the median age of the reported population was 68 years (interquartile range: 61–74 years); the proportion of female patients was higher than that of male patients (56.53% vs 40.56%). The United States submitted the highest number of adverse event reports (n = 15,031, 88.09%), followed by Germany (n = 1076, 6.31%). The median time to onset for adverse event reports was 7.5 days (interquartile range = 0.5–77.5 days); the median time to onset for reports related to alirocumab was 14.5 days (interquartile range = 1.5–100.5 days), while for evolocumab it was only 6.5 days (interquartile range = 0.5–70.5 days). Disproportionate analysis of adverse event reports revealed signals for both evolocumab (ROR = 1.18, 95% CI: 1.16–1.20; information component [IC] = 0.35, IC 025 = 0.33) and alirocumab (ROR = 1.50, 95% CI: 1.45–1.55; IC = 0.41, IC 025 = 0.38). Among these, rhinorrhea, cough, oropharyngeal pain, nasal congestion, and dysphonia were the most frequently reported preferred terms (PTs). The results of this study indicate the presence of a disproportionate signal of RTMD adverse events associated with PCSK9i in the FAERS database; however, this merely suggests that such events warrant further attention in reports related to PCSK9i and does not establish a causal relationship between the 2.