Beta-Blockers After Myocardial Infarction With Preserved and Mildly Reduced Ejection Fraction: A Meta-Analysis With Trial Sequential Analysis

Aims: We aimed to evaluate the efficacy of β-blockers after myocardial infarction (MI) across left ventricular ejection fraction (LVEF) strata and to assess the conclusiveness of the available evidence using trial sequential analysis (TSA). Methods: PubMed, Embase and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) evaluating β-blockers in post-MI patients with LVEF ≥ 40%. A time-to-event meta-analysis was performed for the primary composite (as defined by each trial) and for individual endpoints. The Mantel–Haenszel method was used to pool risk ratios (RR) for major adverse cardiovascular events (MACE; death, MI or heart failure), including LVEF-stratified analyses. TSA estimated the required information size (RIS) and generated adjusted significance and futility boundaries, assuming a 5% type I error and 90% power. Results: Across 19,826 post-MI patients (17,941 with LVEF ≥ 50% and 1885 with LVEF 40%–49%), β-blockers did not reduce time to the primary endpoint (HR 0.92, 95% CI 0.85–1.01; p = 0.08; I2 = 35%) or mortality. In patients with preserved LVEF (≥ 50%), β-blocker therapy did not reduce the risk of death or MACE (RR 0.96, 95% CI 0.87–1.05; I2 = 42%), with TSA confirming futility. Among those with mildly reduced LVEF (40%–49%), β-blockers reduced MACE (RR 0.74, 95% CI 0.58–0.94; I2 = 0%), although TSA failed to establish conclusiveness (RIS of 5717 [14.4%]). A significant interaction by LVEF subgroup was observed for cardiac death (p = 0.03). Conclusions: β-blockers conferred no benefit in post-MI patients with preserved LVEF, with conclusive evidence of futility, whereas therapy was associated with reduced MACE in those with mildly reduced LVEF, pending confirmation in further adequately powered randomized trials.