β-Blockers after myocardial infarction with preserved or mildly reduced left ventricular ejection fraction: Fragility of contemporary evidence

Background β-Blockers have been traditionally prescribed after acute myocardial infarction (MI), but contemporary evidence in patients with preserved or mildly reduced left ventricular ejection fraction (LVEF ≥40%) have not provided consistent results. We assessed the robustness of the evidence for the efficacy of β-blocker therapy in this population using contemporary randomized controlled trials (RCTs) and pooled analyses. Methods We systematically searched PubMed, Scopus, and Embase through August 1, 2025, for phase 3–4 RCTs evaluating β-blockers in patients with LVEF ≥40% during index MI hospitalization. Primary outcomes included robustness of each trial's primary endpoint; secondary outcomes included all-cause and cardiovascular mortality, recurrent MI, heart failure hospitalization, and unplanned revascularization. Fragility index (FI) and fragility quotient (FQ) were calculated. Data were pooled using random-effects meta-analysis. Results Four trials (REDUCE-AMI, CAPITAL-RCT, BETAMI-DANBLOCK, REBOOT) with 19,245 patients were included. Event rates were low across the various outcomes with limited robustness: FI and FQ values indicated high sensitivity to small changes in events. BETAMI-DANBLOCK suggested modest benefit for recurrent MI, while REDUCE-AMI and REBOOT showed no significant effect. Pooled analysis revealed a 9% relative risk reduction and 0.9% absolute risk reduction for the composite of death, recurrent MI, or heart failure hospitalization (number needed to treat = 111; FI = 5). Conclusion In patients with MI and LVEF ≥40%, β-blocker therapy confers only modest absolute benefits, with trial results that are fragile. Routine use in this population may not provide consistent or clinically meaningful benefit, underscoring the need for individualized therapy.