Baseline Ejection Fraction As a Modifier of Beta-Blocker Therapeutic Effects in Post-Acute Coronary Syndrome Patients With Non-Reduced Ejection Fraction: A Systematic Review and Meta-Analysis Publisher Pubmed



Mirhosseini S A ; Sadrzadeh S A ; Semirani Nezhad D ; Rajabi E ; Mohammadi H ; Shaabanpoor Haghighi A ; Jamali M A ; Moshfeghinia R ; Ranjbar M ; Azami P ; Gupta R ; Aronow W S ; Attar A
Source: Cardiovascular Therapeutics Published:2026

Abstract

Background: Beta-blockers are regarded as one of the primary treatment options for acute coronary syndrome (ACS) patients with reduced left ventricular ejection fraction (LVEF). However, there is ongoing debate about their therapeutic efficacy in patients with non-reduced LVEF (≥ 40%). Objective: To determine the impact of long-term beta-blocker administration on major adverse cardiovascular events (MACE) in ACS patients with LVEF ≥ 40%. Methods: A thorough literature search across four databases was conducted to identify eligible studies comparing beta-blocker therapy with placebo or no medication in addition to standard ACS pharmacotherapy. The outcomes of interest included all-cause mortality and MACE (comprising cardiovascular mortality, recurrent myocardial infarction [Re-MI], stroke, rehospitalization for heart failure, and revascularization). Based on LVEF values, patients were divided into three groups: (1) LVEF > 40%, (2) 40% < LVEF < 50%, and (3) LVEF ≥ 50%, and the random-effects meta-analysis estimated the risk ratios (RRs), hazard ratios (HRs), and 95% confidence intervals (CIs). Results: Five randomized controlled trials (RCTs) and 19 observational studies met the inclusion criteria. Within the RCTs, beta-blocker use was associated with a non-significant 6% reduction in MACE (RR = 0.94, 95%CI = 0.87–1.02, I2 = 19.1%). The pooled analyses of observational studies showed no significant overall impact of beta-blocker use on endpoint outcomes. Subgroup analyses revealed a reduction in MACE (HR = 0.75, 95%CI = 0.59–0.95, I2 = 0%) and Re-MI (HR = 0.45, 95%CI = 0.23–0.89) in patients with LVEF 40%–49%; however, these findings were derived primarily from observational data. Patients with LVEF ≥ 50% did not appear to benefit from long-term beta-blocker use. Conclusion: Long-term beta-blocker use did not show a significant benefit in patients with preserved ejection fraction (LVEF ≥ 50%). Observational data suggested a possible reduction in MACE and Re-MI in the LVEF 40%–49% subgroup; however, this finding requires confirmation in dedicated RCTs. Future larger RCTs are needed to clarify the role of beta-blockers in this borderline population. Copyright © 2026 Seyed Alireza Mirhosseini et al. Cardiovascular Therapeutics published by John Wiley & Sons Ltd.