The role of beta-blockers after myocardial infarction (MI) in patients with mildly reduced left ventricular ejection fraction (LVEF) is under debate, after new research was unveiled at the European Society of Cardiology (ESC) Congress 2025.
Two studies presented in a Hot Line session at the ESC, and published simultaneously in The New England Journal of Medicine, gave conflicting findings on the benefit of beta-blocker therapy in patients with LVEF ≥40% post-MI.
In the same session, the Congress also heard the results of a meta-analysis of randomised trials which pointed towards a particular role for beta-blockers for a subgroup of patients with mildly reduced LVEF (40-49%) post-MI.
The REBOOT beta-blocker trial
In the investigator-initiated REBOOT study, which enrolled 8,505 patients with LVEF ≥40% after MI (mean age 61 years; 19.3% women) and randomised them to beta-blockers or no beta-blockers on hospital discharge, researchers found the therapy offered no clinical benefit.
All patients received the current standard of care and were followed for a median of nearly four years, the study authors reported, but there was no significant difference between the two groups in rates of death, reinfarction or hospitalisation for heart failure.
The treatment did seem to benefit a patient subgroup with moderately reduced contractile function, but the sample size was small and underpowered.
Principal investigator Professor Borja Ibáñez, director of clinical research at the Carlos III National Centre for Cardiovascular Research (CNIC) and interventional cardiologist at the Jiménez Díaz Foundation University Hospital, Madrid, Spain, said beta-blockers were a foundational treatment after acute MI, but supporting evidence came from trials predating modern standards of care.
‘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%),’ Professor Ibáñez said.
BETAMI and DANBLOCK
In another study, researchers combined two randomised trials with almost identical designs – BETAMI and DANBLOCK – to assess the effects of beta-blocker therapy on cardiovascular outcomes in patients after MI who had LVEF ≥40% and no clinical heart failure.
This analysis included 5,574 participants (median age 63 years; 20.8% women) randomised to receive either long-term beta-blocker therapy within 14 days of the event or to not receive this therapy.
After a median follow-up of 3.5 years, the incidence of the primary endpoint of all-cause mortality and major adverse cardiovascular events in patients was significantly lower in the beta-blocker group than in the no beta-blocker group (14.2% vs 16.3%).
Although not powered to address the subgroup of patients with mildly reduced LVEF (40-49%), the hazard ratio for the primary endpoint was 0.82 among 854 patients, the researchers reported.
Principal co-investigator Professor Eva Prescott, head of the Centre for Cardiovascular Research at Bispebjerg Frederiksberg University Hospital, Copenhagen, Denmark, said long-term beta-blocker therapy reduced the composite of all-cause mortality and major adverse cardiovascular events in this patient population, with a notable decrease in the incidence of new MI.
‘Our findings suggest that, despite advances in contemporary MI treatment, the beneficial effects of beta-blocker therapy remain clinically relevant, even in patients without reduced LVEF or heart failure,’ she said.
‘However, the results must be considered alongside other recent and ongoing trials of beta-blocker therapy after MI to determine their implications for clinical practice.’
A meta-analysis of beta-blocker data
In the same Hot Line session, researchers presented a meta-analysis of data from patients with mildly reduced LVEF (40-49%) taken from four trials, including REBOOT, BETAMI and DANBLOCK, as well as a previously published trial CAPITAL-RCT.
The analysis, which was simultaneously published in The Lancet, found a significant reduction in the composite of all-cause death, new MI or heart failure with beta-blockers compared with no beta-blockers in this specific group of patients.
Overall, 1,885 patients with mildly reduced LVEF were analysed from the four trials, 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 the therapy.
There was no apparent heterogeneity in the effect on the primary endpoint between the four trials or between the countries of enrolment, the researchers reported.
The three individual components of the primary endpoint followed the same direction as the composite endpoint.
The mildly reduced LVEF subgroup
Speaking on behalf of researchers from the four trials, Dr Xavier Rosselló, clinical scientist at the CNIC and academic clinical cardiologist at Son Espases University Hospital, Palma de Mallorca, Spain, said patients who were post-MI with mildly reduced LVEF (40-49%) but without heart failure represented 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,’ he said.
Dr Rosselló noted that none of the recent randomised trials assessing beta-blockers after a recent MI in patients with LVEF ≥40% was individually powered to assess effects in the mildly reduced LVEF 40-49% subgroup.
‘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%),’ he concluded.
This article was originally published by our sister publication Hospital Healthcare Europe.
