Background <p>In the contemporary reperfusion era, the benefit of beta-blocker therapy in patients after acute myocardial infarction (AMI) and preserved left ventricular ejection fraction (LVEF ≥50%) remains unclear. Recently conducted clinical trials have demonstrated mixed results about the clinical benefit of beta-blockers after myocardial infarction in pooled populations of patients with mildly reduced (LVEF 40–49%) or preserved LVEF. However, new evidence suggests a consistent benefit of beta-blocker therapy in patients specifically with mildly reduced LVEF. We aimed to assess the efficacy of beta-blockers in patients with recent myocardial infarction and mildly reduced or preserved LVEF, as well as specifically with preserved LVEF.</p> Methods <p>We conducted a systematic review of recent randomized controlled trials that evaluated the effects of oral beta-blocker therapy in patients with AMI who had either mildly reduced LVEF or preserved LVEF and with follow-up data of at least 1 year. Using a Mantel-Haenszel random effects model, we computed risk ratios (RR) with 95% confidence intervals for the primary composite outcome along with individual outcomes of death, re-infarction, and heart failure between patients with and without beta-blocker therapy. We performed analysis of the pooled overall study population, which included patients with mildly reduced LVEF and preserved LVEF, as well as performed subgroup analysis of patients with preserved versus mildly reduced LVEF and among men versus women.</p> Results <p>19,826 patients with mildly reduced or preserved LVEF were included in the meta-analysis. Overall, 9,892 patients were assigned to beta-blockers and 9,934 to no beta-blockers. Among the pooled population, we did not demonstrate significant differences between the beta-blocker group and the control group for the primary composite outcome (RR 0.93, 95% CI 0.83–1.04), all-cause death, reinfarction, or heart failure. We further did not detect differences in the primary outcome by sex. While there was no differences in the primary composite outcome among patients with preserved LVEF (RR 0.96, 95% CI 0.86–1.08), there was reduction in risk observed among individuals with mildly reduced LVEF (RR 0.76, 95% CI 0.61–0.94).</p> Conclusion <p>Oral beta-blocker therapy was not associated with a reduction in the primary composite outcome in patients with preserved LVEF. This contrasts with their established benefit in patients with reduced LVEF and the growing evidence of benefit in those with mildly reduced LVEF.</p>