New trial data presented at the ESC 2025 Congress highlights the complexity around beta-blocker therapy after myocardial infarction in patients with an ejection fraction >40%.

The merged BETAMI–DANBLOCK study, concurrently published in the NEJM [link here], found beta-blocker therapy led to a lower risk of death or major adverse cardiovascular events after MI compared to no beta-blocker use after 3.5 years (14.2% v 16.3%; p <0.03).

The study comprised 5,574 patients from 25 sites in Denmark and 19 sites in Norway. Patients with a diagnosis of heart failure or other indications for beta-blocker therapy, as well as contraindications to beta-blocker therapy, were excluded from the study.

However the Spanish-Italian REBOOT-CNIC study, also published in the NEJM [link here], found beta-blocker therapy appeared to have no effect on the incidence of death from any cause, reinfarction, or hospitalisation for heart failure (22.5 events per 1000 patient-years v 21.7 events per 1000 patient-years; HR 1.04; P=0.63).

It comprised 8,505 patients from 109 centres across the two countries and had similar exclusion criteria as the Nordic study. In both studies, the left ventricular ejection fraction was at least 40%.

In both studies, the choice and dose of the beta-blocker were left to the discretion of the treating physician – long-acting versions of metoprolol were mostly prescribed (94.5%) in the BETAMI–DANBLOCK study and bisoprolol was most commonly prescribed (85.9%) in the REBOOT-CNIC study.

Safety endpoints found no significant difference between beta-blocker use and no beta-blocker use in either study.

Meanwhile, a meta-analysis of individual patient data from four trials – REBOOT, BETAMI, DANBLOCK, and CAPITAL-RCT – found beta-blocker therapy was associated with a reduction in the composite of all-cause death, new MI, or heart failure.

The meta-analysis, published in The Lancet [link here], included data from 1,885 patients with mildly reduced LVEF of 40–49%.

“Long-term oral β-blocker therapy was associated with a significant 25% relative reduction in the prespecified primary composite outcome (all-cause death, new myocardial infarction, or heart failure) in patients with myocardial infarction and LVEF of 40–49%,” it said.

However, the three individual components of the primary endpoint, as well as cardiac death, also showed relative reductions without reaching statistical significance. The findings were consistent across all four trials and five countries where patients were enrolled (Spain, Italy, Norway, Denmark, and Japan).

“Overall, our findings support the use of β-blockers in patients with myocardial infarction and mildly reduced LVEF,” it said.

The investigators said their findings aligned with another recent meta-analysis [link here] which showed that beta-blocker therapy was associated with a mortality reduction in patients with MI and mildly reduced LVEF, but not in those with preserved LVEF.

Whether or not to use beta-blockers after MI has already become more nuanced. For example, the Australian clinical guideline for diagnosing and managing acute coronary syndromes 2025 [link here] says:

• In people with ACS and LV impairment, beta-blockers are recommended.
• In people with ACS and preserved LV systolic function who have undergone coronary revascularisation and are receiving optimal medical therapy, consider withholding beta-blockers.

In an editorial accompanying the guidelines [link here], Professor Derek Chew and colleague Dr Timothy Abrahams from the Victorian Heart Institute wrote: “While beta-blockers have historically been a mainstay in post-MI management, recent clinical trial data suggest that their benefits may be limited in patients without reduced ejection fraction.”

“The guideline now reflects a more selective approach, reserving beta-blocker therapy primarily for patients with; reduced ejection fraction (<40%); ongoing ischaemia or arrhythmic risk; persistent hypertension despite optimal medical therapy.”

They said the change “…underscores the emphasis on individualised treatment decisions based on patient-specific risk factors rather than a one-size-fits-all approach.”