Beta-Blockers in Heart Failure With Reduced Ejection Fraction: A Systematic Review of Randomized Controlled Trials

Heart failure with reduced ejection fraction (HFrEF) remains a significant global health burden, with beta-blockers serving as a cornerstone therapy due to their ability to modulate neurohormonal activation and improve outcomes. However, their efficacy in post-myocardial infarction (MI) patients with preserved ejection fraction (EF) remains debated. This systematic review evaluates the clinical effects of beta-blockers in HFrEF and post-MI populations to clarify their role across different patient phenotypes. Eight randomized controlled trials (RCTs) were systematically reviewed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies assessed beta-blockers in HFrEF or post-MI patients, reporting outcomes such as mortality, hospitalizations, or changes in EF. Data were extracted independently by two reviewers, and risk of bias was assessed using the Cochrane RoB 2 tool. A narrative synthesis was performed due to heterogeneity in study designs and interventions. Beta-blockers demonstrated significant reductions in all-cause mortality and heart failure hospitalizations in chronic HFrEF patients. In contrast, they showed neutral effects on mortality and cardiovascular outcomes in post-MI patients with preserved EF. Safety profiles were favorable, with no excess adverse events. Methodological quality was high, with most trials rated as low risk of bias. Beta-blockers are highly effective in HFrEF but offer limited benefits in post-MI patients with preserved EF. These findings support phenotype-specific therapy, reinforcing guideline recommendations for HFrEF while questioning routine use in preserved EF post-MI.