Beta-Blockers in Stable Coronary Artery Disease: A Systematic Review and Meta-Analysis of Observational Studies

The efficacy of beta-blockers in stable coronary artery disease (CAD) patients with preserved left ventricular function remains controversial. We aimed to evaluate the cardiovascular associations of beta-blocker therapy in this population through a comprehensive meta-analysis.

We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, EMBASE, Web of Science, Scopus, Google Scholar, and Cochrane databases from inception to May 2025, updating and extending the previous meta-analysis. We included observational studies comparing beta-blocker therapy versus control in stable CAD patients, defined as those without acute coronary syndrome manifestations for a sufficient period (typically >6 months) to ensure clinical stability, with preserved left ventricular ejection fraction (left ventricular ejection fraction >50%). Primary outcome was cardiac death. Secondary outcomes included all-cause mortality, heart failure, myocardial infarction (MI), and stroke. Random-effects models were used for all analyses. Subgroup analyses were conducted for cardiac and all-cause death stratified by propensity score matching status and prior beta-blocker use exclusion criteria. Publication bias was assessed using funnel plots and Peter's test.

Nine observational studies encompassing 903,870 patients (616,645 beta-blocker users vs. 287,225 controls) were included. Beta-blocker therapy showed no significant association with the primary endpoint: cardiac death (hazard ratio (HR) 0.98, 95% CI: 0.93-1.04, p = 0.54). Secondary outcomes similarly demonstrated no significant associations: all-cause mortality (HR 0.98, 95% CI: 0.91-1.05, p = 0.49), MI (HR 1.02, 95% CI: 0.93-1.11, p = 0.72), stroke (HR 1.02, 95% CI: 0.97-1.08, p = 0.43), and heart failure (HR 1.10, 95% CI: 0.95-1.27, p = 0.20). Substantial heterogeneity was observed for all-cause death (I² = 87%) and heart failure (I² = 95%). Subgroup analyses failed to identify populations with clear associations between beta-blocker therapy and improved outcomes.

Beta-blocker therapy was not significantly associated with cardiovascular benefits in stable CAD patients with preserved left ventricular function. These findings provide additional contemporary evidence supporting current guideline recommendations from both American Heart Association (AHA)/American College of Cardiology (ACC) and European Society of Cardiology (ESC) regarding beta-blocker use in this population. Clinicians should conduct individualized risk-benefit assessments rather than adopting routine prescribing patterns.

CRD420251141812, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=1141812.