β-Blockers Reduce Death, MI, Heart Failure 25% in Mildly Reduced LVEF: Latest Meta-Analysis Presented at ESC Congress 2025

β-blocker therapy results in a 25% reduction in the composite outcome of all-cause death, new myocardial infarction, or heart failure in patients with acute myocardial infarction and mildly reduced left ventricular ejection fraction (40-49%) without history or clinical signs of HF, a recent meta-analysis has reported.

This patient-level meta-analysis pooled data from four RCTs — REBOOT, BETAMI, DANBLOCK, and CAPITAL-RCT — conducted across five countries. It included 1,885 patients with LVEF 40–49% (median age 63 years) who had recent MI (≤14 days) without heart failure, randomized to β-blockers or no β-blockers, with a median follow-up of more than 1 year.​​Of these, 991 patients (53%) were randomized to β-blocker therapy and 894 (47%) to no β-blocker therapy, of whom 991 (53%) were randomized to β-blockers and 894 (47%) to no β-blockers, with a median follow-up of more than 1 year. The major beta-blocker noted in the study was metoprolol (49%). The findings were presented at the recently concluded ESC Congress 2025, Madrid, Spain; and have been published in The Lancet (August 2025).

The primary endpoint included a composite of all-cause death, new myocardial infarction, or heart failure. Key secondary endpoints included the individual components of the primary composite (all-cause death, new MI, heart failure), cardiac death, unplanned coronary revascularization, malignant ventricular arrhythmias, and safety outcomes, including stroke and advanced atrioventricular block.

Key results of the study are

• Primary outcome benefit: Over 3.5 years, β-blockers reduced the composite of death, new MI, or heart failure by 25% (HR 0.75, 95% CI 0.58–0.97; p=0.031), with consistent results across all four trials and countries. (Figure 1)

Figure 1: Cumulative incidence of primary endpoint

• Consistency and sensitivity: No heterogeneity was observed (I²=0%); findings were robust in sensitivity analyses and in patients with LVEF 41–49% (HR 0.73, p=0.037).
• Secondary outcomes: All outcomes trended lower with β-blocker therapy. All-cause death was reduced by 22% with β-blockers (58 vs 69; HR 0.78, 95% CI 0.55–1.11), recurrent MI by 23% (39 vs 46; HR 0.77, 0.50–1.18), heart failure by 29% (30 vs 39; HR 0.71, 0.44–1.14), and cardiac death by 45% (14 vs 23; HR 0.55, 0.28–1.06).
• Safety: Stroke (13 vs 7; HR 1.70, 0.68–4.25), advanced AV block (12 vs 11; HR 1.00, 0.44–2.27), and malignant ventricular arrhythmias (9 vs 5; HR 1.64, 0.55–4.89) were rare, with no significant safety concerns identified
• Subgroups: Benefits were most substantial in patients younger than 75 years, with a 35% lower risk (HR 0.65, 95% CI 0.47–0.90). No heterogeneity was seen by sex, MI type, LVEF subgroup, or country.

Overall, the findings support the use of β-blockers in patients with myocardial infarction and mildly reduced LVEF, highlighting their role as an effective long-term secondary prevention therapy.

This study expands the current evidence on the benefits of initiating β blockers in patients with recent myocardial infarction with reduced LVEF (≤40%) by demonstrating that those with mildly reduced LVEF (40–49%) also derive clinical benefit. Further research should focus on patients with preserved LVEF (≥50%)

Reference: Rossello X, Prescott EIB, Kristensen AMD, Latini R, Fuster V, Fagerland MW, et al. β blockers after myocardial infarction with mildly reduced ejection fraction: an individual patient data meta-analysis of randomised controlled trials. Lancet. 2025 Aug 30. doi: 10.1016/S0140-6736(25)01592-2. [Epub ahead of print]