Impact of beta-blockers after myocardial infarction in patients with preserved or mildly reduced left ventricular ejection fraction: a meta-analysis of randomised trials
L D Neira Chunga, G Vasquez Tirado, D Moncada Gutierrez, M Morales PiscoyaAbstract
Background
Beta-blockers are a cornerstone of secondary prevention following an acute myocardial infarction (AMI), with well-established benefits in patients with reduced left ventricular ejection fraction (LVEF). However, in the contemporary era of early reperfusion and guideline-directed medical therapy, the effectiveness of long-term beta-blocker therapy in patients with preserved or mildly reduced LVEF remains uncertain, as existing evidence is limited and inconsistent.
Purpose
To systematically evaluate the association between beta-blocker therapy and major cardiovascular outcomes in patients with acute myocardial infarction and preserved or mildly reduced left ventricular ejection fraction.
Methods
We conducted a systematic review and meta-analysis of randomised controlled trials in accordance with PRISMA guidelines and prospectively registered in PROSPERO. We searched for studies published up to 30 October 2025 across five electronic databases (PubMed, Embase, Scopus, Web of Science, and ScienceDirect), using a PECO/PICO-based search strategy. Four studies met the inclusion criteria and were included in the quantitative synthesis and meta-analysis. Random-effects meta-analyses were performed using hazard ratios (HRs) with 95% confidence intervals (CIs). The certainty of evidence was assessed using the GRADE approach.
Results
This meta-analysis included four studies comprising a total of 18,504 patients with a history of AMI and an LVEF ≥40%. Among these, 2,223 patients had mildly reduced LVEF, while 15,908 had preserved LVEF. Beta-blocker therapy was not associated with a significant reduction in the primary composite endpoint (all-cause mortality, reinfarction, and cardiovascular hospitalisation) in patients with LVEF ≥40% (HR 0.90; 95% CI 0.81–1.01). Subgroup analyses demonstrated no significant reduction in the primary composite endpoint among patients with preserved LVEF (HR 0.94; 95% CI 0.87–1.03). However, in patients with mildly reduced LVEF, beta-blocker therapy was associated with a significant reduction in the primary composite endpoint (HR 0.82; 95% CI 0.70–0.97).
Conclusions
In this meta-analysis of randomised controlled trials, beta-blocker therapy was not associated with a significant reduction in the primary composite endpoint, nor in individual outcomes such as mortality or reinfarction, among patients with preserved or mildly reduced LVEF following AMI. The apparent benefit observed in patients with mildly reduced LVEF derives from subgroup analysis and should be interpreted with caution within the context of an overall neutral effect.PRISMA flow diagram and Risk of BiasForest plots and sensitivity analyses