Meta-analysis finds that beta-blockers improve outcomes after a heart attack in patients with mildly reduced heart function

Key take-aways

• The effects of beta-blocker therapy in post-myocardial infarction (MI) patients with mildly reduced left ventricular ejection fraction (LVEF 40−49%) are largely unknown.
• A prespecified, individual patient level meta-analysis of four trials demonstrated a significant reduction in the composite of all-cause death, new MI or heart failure with beta-blockers vs. no beta-blockers in this specific group of patients.
• The findings extend the benefits of beta-blockers in patients with MI with reduced LVEF to those with mildly reduced LVEF.

Madrid, Spain - 30 August 2025 : Beta-blocker therapy significantly reduced a composite endpoint of all-cause mortality, new myocardial infarction (MI) and heart failure (HF) compared with no beta-blocker therapy in the subgroup of patients with MI and mildly reduced left ventricular ejection fraction (LVEF), according to an individual patient data meta-analysis presented in a Hot Line session today at ESC Congress 2025.¹ The results have been simultaneously published in The Lancet.

"Patients post-MI with mildly reduced LVEF (40−49%) but without HF represent a sizeable population. While it is intuitive to argue that these patients benefit from beta-blockers in a similar way as patients with reduced LVEF (<40%), there have been no specific randomised trials. Four recent randomised trials tested assessed beta-blockers after a recent MI in patients with LVEF ≥40%; however, none was individually powered to assess effects in the mildly reduced LVEF 40−49% subgroup," explained Doctor Xavier Rosselló from the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain and the Son Espases University Hospital, Palma de Mallorca, Spain, speaking on behalf of the researches from the four trials.

A systematic review was conducted of randomised controlled trials with beta-blockers performed in the reperfusion era (from 2000 onwards) with a median follow-up of more than 1 year in patients with a recent (within 14 days) MI (both ST-elevation MI or non-ST-elevation MI), mildly reduced LVEF and no history or clinical signs of HF. Four trials were identified: REBOOT conducted in Spain and Italy, BETAMI in Norway, DANBLOCK in Denmark and CAPITAL-RCT in Japan. Results from the REBOOT trial² and a combined analysis of the BETAMI and DANBLOCK trials³ were presented in the same Hot Line session today, while CAPITAL-RCT was published in 2018.⁴ In a prespecified, individual patient level meta-analysis across the four trials, a one-stage, fixed-effects approach was used to assess the effect of beta-blockers on the pre-defined primary composite endpoint of all-cause death, new MI or HF. All endpoints were independently adjudicated in all four trials.

Overall, 1,885 patients with mildly reduced LVEF were analysed from the four trials (979 patients from REBOOT, 422 from BETAMI, 430 from DANBLOCK and 54 from CAPITAL-RCT), making up 13.1% of the study populations from the main trials.

The primary endpoint occurred in 10.7% of patients in the beta-blocker group and 14.4% of patients in the no beta-blocker group, representing a significant 25% relative reduction with beta-blockers (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.58 to 0.97; p=0.031). There was no apparent heterogeneity in the effect on the primary endpoint between the four trials or between the countries of enrolment (Spain, Italy, Norway, Denmark and Japan).

The three individual components of the primary endpoint followed the same direction as the composite endpoint. All-cause death occurred in 5.9% and 7.7% of patients in the beta-blocker and no beta-blocker groups, respectively (HR 0.78; 95% CI 0.55 to 1.11). New MI occurred in 3.9% and 5.2% of patients, respectively (HR 0.77; 95% CI 0.55 to 1.11), while HF occurred in 3.0% and 4.4% of patients, respectively (HR 0.71; 95% CI 0.44 to 1.14). In addition, cardiac death was found to occur in 1.8% of patients on beta-blockers and 3.3% of patients with no beta-blockers (HR 0.55; 95% CI 0.28 to 1.06).

Concluding, Doctor Rosselló said: "Our findings extend the known benefits of these agents in MI patients with reduced LVEF to the subgroup with mildly reduced LVEF. Further research should now focus on patients with preserved LVEF (>50%)."

ENDS