Evaluation of Dexmedetomidine-Associated Bradycardia and Related Drug-Drug Interactions Using Electronic Health Record (EHR) and miRNA Target Analysis.

Dexmedetomidine is a commonly used sedative because it has minimal adverse effects on respiratory function. Nevertheless, its cardiovascular safety profile, particularly bradycardia risk and drug-drug interactions (DDIs), remains incompletely understood. Additionally, current studies, including our previous analysis using the FDA adverse event reporting system (FAERS), hold several limitations. In this study, the electronic health record (EHR) platform TriNetX was utilized for pharmacovigilance analyses of dexmedetomidine. The significantly elevated incidence of bradycardia in dexmedetomidine-treated patients was demonstrated compared to other prevalent anesthetics. Age-stratified analyses revealed pronounced susceptibility in geriatric patients, while a slightly increased susceptibility in male patients was observed. In addition, elevated DDIs of dexmedetomidine with risperidone and albuterol were identified using disproportionality analysis with propensity score matching. Finally, to investigate molecular mechanisms of dexmedetomidine-associated bradycardia, analyses were conducted on a public microarray dataset, and nine differentially expressed miRNAs were identified following dexmedetomidine administration. Gene Ontology (GO) analysis of target genes of all five up-regulated miRNAs revealed rhythmic process and muscle tissue development as potential explanations. Notably, the target genes of the up-regulated miRNAs miR-26a-5p and miR-30c-5p were significantly enriched in GO terms associated with bradycardia. Together, this study identified bradycardia as a significant adverse drug event (ADE) of dexmedetomidine administration, observed possible clinically meaningful DDIs with dexmedetomidine, demonstrated a greater risk in elderly patients, and provided transcriptomic evidence that miRNA-mediated pathway dysregulation may contribute to dexmedetomidine-associated bradycardia.