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
Notes to editor
This press release accompanies a presentation at ESC Congress 2025.
It does not necessarily reflect the opinion of the European Society of Cardiology.
Funding: The REBOOT trial was funded by the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) an affiliate centre of the Carlos III Health Institute (ISCIII), an executive agency of the Spanish Ministry of Science, Innovation and Universities. BETAMI was funded by the South-Eastern Norway Regional Health Authority and the Research Council of Norway. DANBLOCK was funded by the Danish Heart Foundation and the Novo Nordisk Foundation. The CAPITAL-RCT trial was funded by an educational grant from the Research Institute for Production Development (Kyoto, Japan).
Disclosures: Doctor Rosselló reports no conflict of interests related to this analysis.
About the study population: In a myocardial infarction (MI; heart attack), one of the coronary arteries becomes blocked and the heart muscle is not supplied with sufficient oxygen. In some patients, the MI can cause long-term damage such that the patient develops heart failure – a condition in which the pumping action of the heart is impaired.
After an MI, the pumping ability of the heart is assessed by measuring the left ventricular ejection fraction (LVEF): the amount of blood that is pumped out of the left ventricle during each heartbeat. An LVEF less than 40% indicates that the heart is pumping weakly and the ejection fraction is said to be ‘reduced’. An LVEF between 40% and 50% indicates slightly impaired pumping abilities and the ejection fraction is said to be ‘mildly reduced’. An LVEF more than 50% indicates that the heart is pumping normally and the ejection fraction is said to be ‘preserved’, although there may still be problems with ventricle stiffening.
References and notes:
1‘REBOOT/BETAMI/DANBLOCK/CAPITAL-RCT: Beta-blockers after MI with mildly reduced EF (an IPD meta-analysis)’ presented during HOT LINE 3 on 30 August 2025 at 11:20 to 11:30 in Madrid (Main Auditorium).
2‘REBOOT-CNIC: Beta-blockers after infarction with LVEF greater than 40%’ presented during HOT LINE 3 on 30 August 2025 at 11:00 to 11:10 in Madrid (Main Auditorium).
3‘BETAMI-DANBLOCK trial: Randomised discontinuation of beta-blockers after myocardial infarction’ presented during HOT LINE 3 on 30 August 2025 at 11:10 to 11:20 in Madrid (Main Auditorium) and simultaneously published in The Lancet.
4Watanabe H, Ozasa N, Morimoto T, et al. Long-term use of carvedilol in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. PLoS One. 2018;13:e0199347.
ESC Press Office
Tel: +33 661401884
Email: press@escardio.org
The hashtag for ESC Congress 2025 is #ESCCongress
Follow us on LinkedIn @European Society of Cardiology News
Journalists are invited to become accredited and register here.
Check out the ESC Media and Embargo Policy.
It is the world’s largest gathering of cardiovascular professionals, disseminating ground-breaking science both onsite in Madrid and online – from 29 August to 1 September 2025. Explore the scientific programme. More information is available from the ESC Press Office at press@escardio.org.
About the European Society of Cardiology
The ESC brings together healthcare professionals from more than 150 countries, working to advance cardiovascular medicine and help people to live longer, healthier lives.