Study of epinephrine-induced cardiovascular adverse events in patients with anaphylaxis using two spontaneously reported adverse event databases from 2004 to 2024

Anaphylaxis is a life-threatening hypersensitivity reaction requiring prompt administration of epinephrine. Despite its life-saving role, hesitancy in epinephrine use persists, largely due to concerns about cardiovascular adverse events (AEs). This study aimed to characterize potentially epinephrine-induced cardiovascular AEs in anaphylaxis using data from two major pharmacovigilance databases. A retrospective analysis was conducted using individual case safety reports (ICSRs) from the US FDA Adverse Event Reporting System (FAERS) and the European EudraVigilance database from 2004 to 2024. ICSRs were included if epinephrine was a suspect drug and the indication involved anaphylaxis or related terms. Reports were screened for cardiovascular AEs and assessed for causality by two independent reviewers. Descriptive statistics were used to summarize findings. A total of 802 and 517 ICSRs were analyzed from FAERS and EudraVigilance, respectively. Cardiovascular AEs were reported in 142 and 134 ICSRs, respectively, with epinephrine as the sole suspect in most cases. Female patients were more frequently represented. Stress cardiomyopathy, myocardial ischemia, tachycardia, and acute myocardial infarction were the most common cardiovascular AEs. Intravenous administration was frequently associated with serious outcomes. Causality assessment indicated that a majority of cardiovascular AEs were likely related to epinephrine. Cardiovascular AEs, particularly stress cardiomyopathy, are associated with epinephrine use in anaphylaxis, especially when administered intravenously. While these findings support cautious use, they also highlight the importance of adhering to recommended intramuscular administration to minimize preventable risks. Clinician awareness and adherence to guidelines remain critical for safe and effective anaphylaxis management, prioritizing cautious use over hesitancy.