Cardiovascular Adverse Event Reporting Patterns for Atenolol, Bisoprolol, and Nebivolol: A Pharmacovigilance Disproportionality Analysis of the FDA Adverse Event Reporting System

Abstract

Background: Beta-blockers are widely prescribed across cardiovascular indications, yet their real-world cardiovascular adverse-event profiles across drug generations remain incompletely characterised in large pharmacovigilance datasets. Objective: The objective was to describe and compare cardiovascular adverse-event reporting patterns for atenolol, bisoprolol and nebivolol in the FDA Adverse Event Reporting System (FAERS). Methods: We performed a retrospective disproportionality analysis of FAERS reports using OpenVigil 2.1, covering each drug’s available reporting history from the first quarter of 2004 (2007 for nebivolol) through the third quarter of 2025 (FAERS 2025 Q3). Cardiovascular events were defined as individual MedDRA Preferred Terms; signals were assessed with the Reporting Odds Ratio (ROR, 95% CI) and Information Component (IC) under Evans’ criteria. Individual case safety reports were also analysed for demographics, seriousness and outcomes. Results: Atenolol was most strongly associated with bradycardia (ROR = 10.513), followed by pericardial haemorrhage (ROR = 7.067) and ventricular hypertrophy (ROR = 6.999). Bisoprolol showed the highest signals for diastolic dysfunction (ROR = 24.875), atrial tachycardia (ROR = 23.283) and chronic cardiac failure (ROR = 23.222). Nebivolol had the lowest overall reporting volume, although counts were not adjusted for exposure; its strongest signals were bradycardia (ROR = 9.619) and coronary artery stenosis (ROR = 9.351). Paediatric reports (0–17 years) were uncommon for atenolol and bisoprolol and nearly absent for nebivolol; none of the three is FDA-approved in this group. Reports mainly involved older adults (60–89 years), and a substantial proportion were classified as serious. Conclusions: All three agents generated significant signals across a broad range of cardiovascular events. Nebivolol had the lowest reporting volume, but this should not be interpreted as evidence of a safer profile. Because FAERS disproportionality cannot establish causality, these findings are hypothesis-generating and require prospective confirmation before they can inform beta-blocker selection.