Study title: REBOOT/BETAMI/DANBLOCK/CAPITAL-RCT: Beta-Blockers after MI with Mildly Reduced EF (an IPD meta-analysis)

Presented at Congress: ESC Congress 2025 – Hot Line 3

Link: https://esc365.escardio.org/presentation/312161

Prepared by: Dr. Mehmet Murat Yiğitbaşı

Introduction
The benefits of beta-blockers after myocardial infarction (MI) are well established in patients with reduced left ventricular ejection fraction (LVEF <40%). However, in patients with mildly reduced LVEF (40–49%) and no clinical heart failure, the long-term effects of beta-blocker therapy have been uncertain.

Objective
To evaluate the effect of beta-blockers on the composite of all-cause death, new MI, or heart failure in patients with recent MI, mildly reduced LVEF (40–49%), and no history/signs of heart failure, by pooling individual patient data (IPD) from contemporary randomized trials.

Methods
Prespecified IPD meta-analysis including four randomized trials conducted in the reperfusion era: REBOOT (Spain/Italy), BETAMI (Norway), DANBLOCK (Denmark), and CAPITAL-RCT (Japan). Eligibility: randomization within 14 days after MI; LVEF 40–49%; no history or signs of heart failure; median follow-up >1 year; oral beta-blocker strategy versus no beta-blocker. A one-stage fixed-effects model was used to estimate the treatment effect on the predefined primary composite endpoint of all-cause death, new MI, or heart failure.

Results
A total of 1,885 patients were analyzed (REBOOT n=979; BETAMI n=422; DANBLOCK n=430; CAPITAL-RCT n=54). The primary composite endpoint occurred in 10.7% with beta-blockers versus 14.4% with no beta-blocker, yielding a 25% relative risk reduction (HR 0.75; 95% CI 0.58–0.97; p=0.031). No meaningful heterogeneity was observed across trials or enrolling countries. Component endpoints showed concordant trends: all-cause death 5.9% vs 7.7% (HR 0.78; 95% CI 0.55–1.11), new MI 3.9% vs 5.2% (HR 0.77; 95% CI 0.55–1.11), and heart failure 3.0% vs 4.4% (HR 0.71; 95% CI 0.44–1.14). Cardiac death showed a numerical reduction (1.8% vs 3.3%; HR 0.55; 95% CI 0.28–1.06).

Conclusion
In post-MI patients with mildly reduced LVEF (40–49%) and no clinical heart failure, long-term beta-blocker therapy significantly reduced the composite of all-cause death, new MI, or heart failure compared with no beta-blocker therapy, extending the evidence base from reduced LVEF into the mildly reduced range.

Commentary
These findings support sustained beta-blocker therapy after MI in the 40–49% LVEF subgroup. Uncertainty remains for patients with preserved LVEF >50%, warranting additional dedicated trials. Treatment decisions should consider contraindications (e.g., bradycardia, hypotension, conduction disease, bronchospasm) and individual tolerability.