Madrid, Spain – 30 August 2025: Beta-blocker therapy showed no evidence of an effect on all-cause death, reinfarction or heart failure admission in patients with myocardial infarction (MI) managed invasively who had left ventricular ejection fraction (LVEF) ≥40%, according to late-breaking research from the REBOOT trial presented in a Hot Line session today at ESC Congress 20251 and simultaneously published in the New England Journal of Medicine.
Explaining the rationale for the REBOOT trial, Principal Investigator, Professor Borja Ibáñez from the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) and Fundación Jiménez Díaz University Hospital, Madrid, Spain, said: “Beta-blockers have long been a foundational treatment after acute MI; however, supporting evidence is derived from trials that predate modern standards of care − before the time of routine reperfusion, invasive management, potent antiplatelet therapies and statins. Re-examining the role of beta-blockers is warranted, particularly among patients with uncomplicated MI and LVEF >40% in whom the benefits of beta-blockers are not well established, unlike with reduced LVEF (≤40%).”
The investigator-initiated randomised open blinded-endpoint REBOOT trial was conducted at 109 centres across Spain and Italy. Patients with MI (with or without ST-segment elevation) were eligible for enrolment if they underwent invasive management during the index hospitalisation and had a predischarge LVEF >40%, with no history or signs of heart failure. Patients were randomised 1:1 to beta-blocker or no beta-blocker therapy. The primary endpoint was a composite of all-cause mortality, nonfatal reinfarction or heart failure admission.
Among 8,505 patients who underwent randomisation, the mean age was 61 years and 19.3% were women. A total of 10% had a prior MI and 12% were on beta-blocker treatment before the index hospitalisation.
After a median follow-up of 3.7 years, the primary composite outcome of all-cause death, nonfatal reinfarction or heart failure admission occurred in a similar proportion of patients in each group: 22.5/1,000 patient-years in beta-blocker group and 21.7/1,000 patient-years in the no beta-blocker group (hazard ratio [HR] 1.04; 95% confidence interval [CI] 0.89 to 1.22; p=0.63).
All-cause mortality occurred in 11.2 and 10.5/1,000 patient-years on beta-blocker therapy and no-beta blocker therapy, respectively (HR 1.06; 95% CI 0.85 to 1.33). Nonfatal reinfarction occurred in 10.2 and 10.1/1,000 patient-years, respectively (HR 1.01; 95% CI 0.80 to 1.27), while heart failure admission occurred in 2.7 and 3.0/1,000 patient-years, respectively (HR 0.89; 95% CI 0.58 to 1.38).
Regarding safety, admission for stroke occurred in 2.6/1,000 patient-years in the beta-blocker group and 1.7/1,000 patient-years in the no beta-blocker group (HR 1.50; 95% CI 0.90 to 2.49). Admission for symptomatic advanced atrioventricular block occurred in 0.5 of patients in the beta-blocker group and 0.4/1,000 patient-years of patients in the no beta-blocker group (HR 1.18; 95% CI 0.40 to 3.50).
There appeared to be an absence of benefit with beta-blockers across the prespecified subgroups. However, fewer events were noted in patients with mildly reduced LVEF (40−49%) on beta-blockers vs. no beta-blockers, although low patient numbers limit interpretability. Women experienced overall more events, especially when on beta-blockers.
Professor Ibáñez concluded: “Beta-blocker therapy showed no evidence of benefit across the study population of patients with MI managed invasively who had LVEF >40%. However, as also presented today at ESC Congress, a meta-analysis of data from four trials, including REBOOT, suggest there may be a positive signal in patients with mildly reduced LVEF (40−49%).2”
ENDS
This press release accompanies both a presentation and an ESC press conference at ESC Congress 2025.
It does not necessarily reflect the opinion of the European Society of Cardiology.
Notes to editor
Funding: The 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 of Spain. The clinical trial was carried out with the collaboration of the Spanish Society of Cardiology (SEC) and the Spanish cardiovascular research network, CIBERCV.
Disclosures: Professor Ibáñez has no disclosures to report related to this trial.
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-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).
2‘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) and simultaneously published in New England Journal of Medicine.
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