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

Q: What is the clinical evidence from this study?

Study design: Observational. Population: Cardiovascular adverse events associated with beta-blocker therapy (n=16320000). Intervention: Atenolol, bisoprolol, and nebivolol vs. All other drugs in the FAERS database. Primary outcome: Disproportionate reporting of cardiovascular adverse events (strongest signal overall: diastolic dysfunction with bisoprolol) (OR 24.875, 95% CI 21.966-28.168).

Q: What does this research mean for the field?

In real-world pharmacovigilance reporting, atenolol, bisoprolol, and nebivolol are associated with distinct cardiovascular adverse event profiles, with atenolol and nebivolol showing predominant signals for bradycardia and bisoprolol demonstrating strong signals for diastolic dysfunction, atrial tachycardia, and chronic cardiac failure. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Matthew Nho; Vinay Kumar; Hema Vathy; Ravi Prakash; Ahmed Abdel‐Latif; Anand Prakash Singh

doi:10.3390/cardiovascmed29040041

October 20, 2026Cardiovascular MedicineOpen Access

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

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Key result

Bisoprolol is linked to ~24.9-fold higher odds of reported diastolic dysfunction in FAERS.

OR 24.875
95% CI 21.966-28.168
n=16,320,000

Why the study?

Beta-blockers are widely prescribed across cardiovascular indications, yet their real-world cardiovascular adverse-event profiles across drug generations remain incompletely characterized in large pharmacovigilance datasets.

How do the real-world cardiovascular adverse-event reporting profiles compare among atenolol, bisoprolol, and nebivolol in the FDA Adverse Event Reporting System?

Key Points

To compare the real-world cardiovascular safety and adverse-event reporting profiles of atenolol, bisoprolol, and nebivolol using the FDA Adverse Event Reporting System.
Retrospective pharmacovigilance disproportionality analysis of FAERS safety reports through January 1, 2026, using OpenVigil 2.1.
Cardiovascular adverse events identified via Standardized MedDRA Queries and evaluated using Reporting Odds Ratios (ROR, 95% CI) and Information Components under Evans' criteria.
Atenolol showed its strongest disproportionality signals for bradycardia (ROR = 10.513) and left ventricular hypertrophy (ROR = 6.765).
Bisoprolol generated the highest signals for diastolic dysfunction (ROR = 24.875), atrial tachycardia (ROR = 23.283), and chronic cardiac failure (ROR = 23.222), alongside a 14.9% bradycardia-associated mortality rate.
Nebivolol exhibited the lowest overall reporting burden, with primary signals for bradycardia (ROR = 9.619) and coronary artery stenosis (ROR = 9.351), with a 12.6% bradycardia-associated mortality rate.

Study Design

Type

Observational (n=16,320,000)

Multicenter

Yes

Structured PICO

How do the real-world cardiovascular adverse-event reporting profiles compare among atenolol, bisoprolol, and nebivolol in the FDA Adverse Event Reporting System?

P

Population

Approximately 16.32 million individual case safety reports in the FAERS database from 2004 to 2025 Q3, predominantly involving older adults aged 60–89 years, evaluated for cardiovascular adverse events associated with atenolol, bisoprolol, and nebivolol.

E

Exposure

Atenolol, bisoprolol, and nebivolol

C

Comparator

Head-to-head comparison among atenolol, bisoprolol, and nebivolol, and disproportionality comparison against background FAERS reports

O

Outcome

Cardiovascular adverse events identified via Standardized MedDRA Queries, assessed using Reporting Odds Ratio (ROR) and Information Component (IC) through January 1st, 2026safety

Main Result

Odds Ratio: 24.875 (95% CI 21.966–28.168)

Limitations

Voluntary reporting in FAERS leads to underreporting and prevents estimation of true incidence or causality.
Confounding by indication and channelling bias, particularly for bisoprolol in heart failure patients.
Inability to account for concomitant medications, polypharmacy, dose, or treatment duration.
Differences in market penetration, prescribing volume, and duration of clinical availability limit direct cross-drug comparisons.
Potential duplicate entries and variable data quality inherent to voluntary submissions.
Lack of external validation in other spontaneous reporting systems (e.g., VigiBase) or longitudinal cohorts.
Lack of reliable patient ethnicity data and inability to stratify by pregnancy or lactation status.
Comparisons were made against the whole FAERS background rather than head-to-head among the three beta-blockers.
Report counts are not exposure-adjusted
FAERS disproportionality analysis cannot establish causality
Findings are hypothesis-generating and require prospective confirmation

Implication

In a FAERS pharmacovigilance analysis, atenolol, bisoprolol, and nebivolol all generated significant cardiovascular adverse event signals, with nebivolol demonstrating the most favorable reporting profile and bisoprolol showing strong signals for diastolic dysfunction, atrial tachycardia, and chronic cardiac failure.

Abstract

Background: Beta-blockers are widely prescribed across cardiovascular indications, yet their real-world cardiovascular adverse-event profiles across drug generations remain incompletely characterized in large pharmacovigilance datasets. Objective: To compare the cardiovascular safety profiles of atenolol, bisoprolol and nebivolol using the FDA Adverse Event Reporting System (FAERS). Methods: Retrospective disproportionality analysis of FAERS reports via OpenVigil 2.1, covering each drug’s available reporting history through January 1st, 2026. Cardiovascular events were identified with Standardized MedDRA Queries; signals were assessed with the Reporting Odds Ratio (ROR, 95% CI) and Information Component (IC) under Evans’ criteria. Individual case safety reports were analysed for demographics, seriousness and outcomes. Results: Atenolol was most strongly associated with bradycardia (ROR = 10.513) and left ventricular hypertrophy (ROR = 6.765). Bisoprolol showed the highest signals for diastolic dysfunction (ROR = 24.875), atrial tachycardia (ROR = 23.283) and chronic cardiac failure (ROR = 23.222), together with the highest bradycardia-associated mortality (14.9%). Nebivolol had the lowest overall reporting burden, though counts are not exposure-adjusted; its strongest signals were bradycardia (ROR = 9.619) and coronary artery stenosis (ROR = 9.351), with lower bradycardia mortality (12.6%). Pediatric reports (0–17 years) occurred for all three agents at similar proportions, none FDA-approved in this group. Reports predominantly involved older adults (60–89 years), with a substantial proportion classified as serious. Conclusion: All three agents generated significant signals across a broad range of cardiovascular events, with nebivolol showing the most favourable profile. Because FAERS disproportionality cannot establish causality, these hypothesis-generating findings may inform beta-blocker selection in older or higher-risk patients, particularly those prone to bradyarrhythmias or diastolic dysfunction, pending prospective confirmation.

Discussion

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Cite This Study

Nho et al. (2026) conducted an observational in Cardiovascular adverse events associated with beta-blocker therapy (n=16,320,000). Atenolol, bisoprolol, and nebivolol vs. All other drugs in the FAERS database was evaluated on Disproportionate reporting of cardiovascular adverse events (strongest signal overall: diastolic dysfunction with bisoprolol) (OR 24.875, 95% CI 21.966-28.168). Atenolol, bisoprolol, and nebivolol showed strong FAERS signals for bradycardia (ROR 10.513), diastolic dysfunction (ROR 24.875), and bradycardia (ROR 9.619), respectively.

synapsesocial.com/papers/6ae28dedcbadf70daf6c3f25 https://doi.org/10.3390/cardiovascmed29040041

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

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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