Beta-blocker therapy following myocardial infarction (MI) was the primary focus of a hot line session at ESC Congress 2025. Study investigators presented findings from the REBOOT-CNIC and BETAMI-DANBLOCK trials, as well as a larger meta-analysis of REBOOT, BETAMI, DANBLOCK and CAPITAL-RCT.

"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," said Borja Ibáñez, MD, PhD, who presented the REBOOT-CNIC findings. "Re-examining the role of beta-blockers is warranted."

In REBOOT-CNIC, simultaneously published in NEJM, beta-blocker therapy following acute MI in patients with mildly reduced or preserved ejection fraction (>40%) did not reduce the incidence of death from any cause, reinfarction or hospitalization for heart failure (HF).

The trial randomized approximately 8,000 patients with MI from 109 centers across Spain and Italy to beta-blocker or no beta-blocker therapy. All patients (with or without ST-segment elevation) underwent invasive management for MI and had a predischarge LVEF >40%, with no history or signs of HF. The mean participant age was 61 years, 19.3% were women and 10% had experienced a previous MI.

"Beta-blocker therapy showed no evidence of benefit across the study population of patients with MI managed invasively who had LVEF >40%," said Ibáñez. "However, there may be a positive signal in patients with mildly reduced LVEF (40−49%)."

The study investigators did observe higher rates of primary-outcome events among women, as well as patients with STEMI, assigned to beta-blockers vs. no beta-blockers. However, they note that "these possible signals of harm should be interpreted with caution and considered to be hypothesis-generating."

In the BETAMI-DANBLOCK study, also simultaneously published in NEJM, beta-blocker therapy in patients with an MI and an LVEF of at least 40% led to a lower risk of death or major adverse cardiovascular events, compared with no beta-blocker therapy at all.

The study – a combination of the Norwegian BETAMI and the Danish DANBLOCK trial – compared beta-blocker therapy with no beta-blocker therapy in approximately 5,500 patients after MI who had LVEF ≥40% and no clinical diagnosis of HF. After a median follow-up of 3.5 years, the incidence of all-cause mortality and major cardiovascular events was significantly lower in the beta-blocker group than in the no beta-blocker group (14.2% vs. 16.3%, respectively).

"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 [HF]," said Eva Prescott, MD, DMSc, the study's principal investigator. "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."

Adding to the new data, a meta-analysis of REBOOT, BETAMI, DANBLOCK and CAPITAL-RCT trials simultaneously published in The Lancet found beta-blocker therapy was associated with a significant reduction in the incidence of the composite outcome of all-cause death, new MI or HF in patients with MI and mildly reduced LVEF.

According to the study authors, the primary endpoint occurred in 10.7% of patients in the beta-blocker group and 14.4% of patients assigned to no beta-blockers, representing a significant 25% relative reduction with beta-blockers. "There was no apparent heterogeneity in the effect on the primary endpoint between the four trials or between the countries of enrollment (Spain, Italy, Norway, Denmark and Japan)," they said.

"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 randomized trials," said Xavier Rosselló, MD, PhD, speaking on behalf of the researchers from the four trials. "…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%)."