Beta-Blockers After MI in Patients with LVEF Above 40%: Findings of BETAMI-DANBLOCK Trial Presented at ESC Congress 2025

Beta-blocker therapy reduced the risk of death or major adverse cardiovascular events by 15% in patients with MI and a LVEF above 40%, a recently published BETAMI-DANBLOCK combined trial has reported.

The Combined Trial (BETAMI – Norwegian Beta-Blocker Treatment after Acute Myocardial Infarction in Revascularized Patients without Reduced LVEF, and DANBLOCK – Danish Trial of Beta-Blocker Therapy after Myocardial Infarction without Heart Failure) was a superiority trial with a PROBE design (Prospective, Randomized, Open-label, Blinded Endpoint Evaluation) conducted across 44 sites in Norway and Denmark. It included 5,574 patients with LVEF ≥40% in BETAMI (with mandatory coronary revascularization) or >40% in DANBLOCK (no revascularization requirement) who were randomized in a 1:1 ratio to receive either long-term beta-blocker therapy (n=2,783) or no beta-blocker therapy (n=2,791) within 7 days in BETAMI and 14 days in DANBLOCK after MI. The choice of drug included metoprolol, bisoprolol, carvedilol, or nebivolol, with investigators advised to use the maximum tolerated dose. However, it is noteworthy that ~94% patients received metoprolol in the study.

The findings were presented at the recently concluded ESC Congress 2025, Madrid, Spain, and have been published in the New England Journal of Medicine (August 2025).

The primary outcome was a composite of death, new MI, revascularization, ischemic stroke, heart failure, or malignant ventricular arrhythmias, with secondary endpoints including individual components and safety outcomes assessed after a median follow-up of 3.5 years.

The key findings of the study include

Primary Composite Endpoint Benefit: Beta-blocker therapy reduced the risk of death or MACE (new MI, unplanned coronary revascularization, ischemic stroke, heart failure, or malignant ventricular arrhythmias) by 15% (HR 0.85; 95% CI 0.75–0.98; P=0.03). Events occurred in 14.2% patients on beta-blockers vs 16.3% without beta-blockers.

Figure: Primary endpoint: composite of death, myocardial infarction, unplanned revascularization, stroke, heart failure, or malignant arrhythmias. (image will be recreated once client approves)

Prevention of New MI: Beta-blockers reduced the risk of new myocardial infarction by 27% (HR 0.73; 95% CI 0.59–0.92). Among these events, most were non-STEMIs (80%), and two-thirds occurred in revascularized patients.

Mortality and other CV Outcomes: Mortality was slightly lower with beta-blocker therapy (4.2% vs 4.4%), corresponding to a 6% relative risk reduction (HR 0.94; 95% CI 0.73–1.21). Other individual endpoints showed lower event rates with beta-blockers, including a 28% reduction in heart failure (1.5% vs 1.9%, HR 0.78) and an 18% reduction in malignant arrhythmias (0.5% vs 0.6%, HR 0.82).

Subgroup and Time-to-Benefit Analyses: The primary endpoint event benefits were consistent across subgroups: age <70 years 18% reduction (HR 0.82), STEMI 19% reduction (HR 0.81), mildly reduced LVEF 40–49% 18% reduction (HR 0.82). Benefit appeared early and persisted: at 12 months, events were (5.3%) vs 181/2,791 (6.5%), a 20% reduction (HR 0.80).

Treatment, Adherence, and Safety: At 6 months, adherence was similar (88.6% vs 88.7%). Safety profile was excellent: 30-day safety events were 0.8% vs 1.1%, pacemaker/AV block identical at 1.8% each (HR 1.00), and serious adverse events were comparable.

Consistent Benefit in the Background of Effective Secondary Therapies: Importantly, benefits were demonstrated despite widespread use of therapies including revascularization (94.5%), aspirin (95.0%), P2Y12 inhibitors (88.6%), and statins (97.3%).

Interestingly, the researchers noted that nearly all patients in this trial received treatment with long-acting versions of metoprolol at a median starting dose of 50 mg; therefore, the findings may not be generalizable to other beta-blocker classes and higher doses.

This BETAMI-DANBLOCK trial demonstrates that oral beta-blocker therapy led to a lower risk of death or MACE than no beta-blocker therapy among patients with MI and preserved or mildly reduced LVEF.

Abbreviations: MI – Myocardial Infarction, LVEF – Left Ventricular Ejection Fraction, BETAMI – Norwegian Beta-Blocker Treatment after Acute Myocardial Infarction in Revascularized Patients without Reduced Left Ventricular Ejection Fraction, DANBLOCK – Danish Trial of Beta-Blocker Therapy after Myocardial Infarction without Heart Failure, PROBE – Prospective, Randomized, Open-label, with Blinded Endpoint Evaluation, MACE – Major Adverse Cardiovascular Events, STEMI – ST-Elevation Myocardial Infarction, IQR – Interquartile Range, AV block – Atrioventricular Block, HR – Hazard Ratio, CI – Confidence Interval, P2Y12 inhibitors – Platelet P2Y12 Receptor Inhibitors.

Reference: Munkhaugen J, Kristensen AMD, Halvorsen S, et al, for the BETAMI–DANBLOCK Investigators. Beta-Blockers after Myocardial Infarction in Patients without Heart Failure. N Engl J Med. 2025;DOI: 10.1056/NEJMoa2505985. Published online August 30, 2025.