Long-term outcomes of beta-blockers in post-MI patients with mildly reduced or preserved left ventricular ejection fraction: a systematic review and meta-analysis

Background Beta-blockers improve survival in post–myocardial infarction (MI) patients with reduced left ventricular ejection fraction (LVEF). However, their benefit in patients without reduced LVEF remains uncertain. Methods We conducted a systematic review and meta-analysis of studies reporting long-term outcomes of beta-blocker therapy in post-MI patients with LVEF>40%, searching PubMed, Scopus, Embase, and Cochrane databases through October 2025. Conventional meta-analysis was performed using a random-effects model to pool hazard ratios (HRs) with 95% confidence intervals (CIs). In parallel, cox proportional hazards frailty models and restricted mean survival time (RMST) analyses were performed using reconstructed time-to-event individual patient data (IPD). The primary endpoint was all-cause mortality. Secondary endpoints included cardiovascular mortality, major adverse cardiovascular events (MACEs) and their components (e.g., recurrent MI, heart failure, revascularization, and stroke). Prespecified subgroup analyses stratified patients by LVEF (40–50% vs. >50%) and study design (RCTs vs. cohort studies). Results A total of 150,182 patients from 4 randomized controlled trials (RCTs) and 20 cohort studies were included, with a mean age of 63.6 years and 23.8% female. The median follow-up was 3.5 years (interquartile range, 2.0–4.75). Of the 151,182 patients included in the analysis, 108,497 were treated with beta-blockers, whereas 41,685 did not receive beta-blocker therapy. Among patients with LVEF >40%, beta-blocker therapy was associated with lower all-cause mortality (HR 0.82; 95% CI 0.73–0.93; P < 0.001; I² = 62%). No significant differences were observed for secondary endpoints. Mortality reduction was confined to patients with LVEF 40–50% (HR 0.70; 95% CI 0.50–0.98) and was not observed in those with LVEF >50% (HR 0.82; 95% CI 0.60–1.20). Reconstructed IPD analyses confirmed reduced all-cause mortality (HR 0.69; 95% CI 0.66–0.73; P < 0.001) and cardiovascular mortality (HR 0.52; 95% CI 0.48–0.57; P < 0.001), but not recurrent MI (HR 0.96; 95% CI 0.90–1.01; P = 0.115) in patients without reduced LVEF. Subgroup analysis indicated that mortality benefits were driven by cohort studies, with no significant effect observed in RCTs. Conclusion In post-MI patients with LVEF>40%, beta-blocker therapy confers a survival benefit in those with LVEF 40–50% but not in patients with LVEF >50%. Secondary endpoints were unaffected by beta-blocker therapy. These findings suggest that routine use of beta-blockers in post-MI patients with preserved LVEF may not provide additional mortality or morbidity benefits. Further randomized studies are warranted to clarify the role of beta-blockers in this population.