Overview

• REBOOT, an independent randomized trial of 8,505 patients in Spain and Italy, found no reduction in death, recurrent myocardial infarction, or heart failure hospitalization with beta-blockers when left ventricular ejection fraction exceeded 40%.
• A prespecified REBOOT analysis reported worse outcomes for women on beta-blockers, including a 2.7 percentage point higher absolute mortality over roughly 3.7 years, concentrated in those with ejection fraction of 50% or higher.
• Investigators noted that women in REBOOT were older, had more comorbidities, and were less often prescribed some secondary prevention therapies, underscoring caution in interpreting the female harm signal.
• The BETAMI–DANBLOCK trial in Norway and Denmark observed fewer nonfatal recurrent heart attacks with beta-blockers without a mortality difference, and pooled analyses indicate benefit for patients with ejection fraction of 40–49%.
• Experts and trial leaders are urging guideline reassessment toward ejection‑fraction–stratified and sex‑specific prescribing, as routine use after uncomplicated infarction faces new scrutiny and formal updates are pending.