Beta-blockers after myocardial infarction with preserved ejection fraction: A meta-analysis with trial sequential analysis

Background

The role of beta-blockers after myocardial infarction (MI) in patients with preserved ejection fraction remains controversial.

Methods

We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library from their inception to September 2025 for relevant randomized controlled trials (RCTs). The primary endpoint was a composite outcome comprising all-cause deaths, recurrent myocardial infarction, hospitalization for heart failure, and stroke. Risk ratios (RRs) with corresponding 95% confidence intervals (CIs) were calculated as the primary effect estimates.

Results

Five RCTs involving 23524 patients with MI and preserved ejection fraction were included. Pooled results showed that no significant difference was detected between beta-blockers therapy and treatments with no beta-blockers on the composite outcome (RR,0.93; 95% CI,0.84–1.03). However, metoprolol was associated with a modest but statistically significant risk reduction (RR,0.89; 95% CI,0.80–0.99). Beta-blocker therapy did not confer significant reductions on all-cause death, cardiovascular death, myocardial infarction, hospitalization for heart failure, stroke or compared with no beta-blocker use.

Conclusions

In patients with MI and preserved ejection fraction, beta-blocker therapy did not significantly reduce the risk of composite or individual clinical outcomes compared with no beta-blockers use. Notably, metoprolol showed a modest but significant benefit, suggesting that potential agent-specific effects warrant further investigation.

Trial registration: PROSPERO (CRD420251149074)