In patients with myocardial infarction and preserved left ventricular function, beta-blocker therapy was associated with a lower risk of death or major adverse cardiovascular events compared with no therapy, according to results from the BETAMI–DANBLOCK trial, the largest contemporary randomized study to provide evidence in the modern reperfusion era.
The trial enrolled 5,574 patients with myocardial infarction (MI) and left ventricular ejection fraction (LVEF) at least 40%. The primary composite endpoint occurred in 14% of patients assigned to beta-blockers vs 16% of those without, a 15% relative risk reduction (hazard ratio, 0.85), corresponding to an absolute risk reduction of nearly 2 percentage points.
The evidence supporting beta-blocker therapy following MI was established before modern coronary reperfusion therapy and secondary prevention strategies. These findings, published in the New England Journal of Medicine, represent the largest contemporary randomized evidence supporting existing recommendations since modern MI care became standard.
Largest Contemporary Trial
This open-label, randomized trial with blinded endpoint evaluation enrolled patients from 44 sites across Denmark and Norway between October 2018 and January 2024. A total of 2,783 patients were randomized to beta-blockers and 2,791 to no therapy within 7 to 14 days following MI (7 days in BETAMI; 14 days in DANBLOCK). BETAMI enrolled type 1 MI only, whereas DANBLOCK included type 1 or type 2 MI. Independent endpoint committees, blinded to treatment assignment, validated all components of the endpoint except all-cause mortality. Follow-up was registry based to enhance completeness and generalizability.
The primary endpoint was a composite of death or major adverse cardiovascular events (MACE) (new MI, unplanned coronary revascularization, ischemic stroke, heart failure, or malignant ventricular arrhythmias).
After a median follow-up of 3.5 years, the 15% relative risk reduction was driven largely by fewer recurrent MIs (5.0% vs 6.7%). At 12 months, the primary outcome from sensitivity analysis also favored beta-blockers (HR 0.80).
Modern Patient Population
Patients reflected contemporary MI care: 94.5% underwent revascularization, and nearly all received evidence-based secondary prevention (aspirin 95%, P2Y12 blockers 89%, statins 97%). Median age was 63 years; 21% were women; 48% had ST-segment elevation MI; and 85% had LVEF at least 50%. Prior coronary disease was present in 11%, and 8% were receiving beta-blockers at enrollment.
Long-acting metoprolol was prescribed in about 95% of patients assigned to beta-blockers, with a median starting dose of 50 mg. Adherence to the assigned strategy remained high at 6 months (88.6% vs 88.7%).
Secondary Endpoints
Death from any cause occurred in approximately 4.2% vs 4.4%. Heart failure events and unplanned coronary revascularization were similar between groups. Ischemic stroke occurred in approximately 1.6% vs 1.3%, and malignant ventricular arrhythmias in approximately 0.5% vs 0.6%.
Subgroups and Safety
Prespecified subgroup analyses showed consistent effects across sex, age, country, MI type, and ejection-fraction categories. A 30-day composite safety endpoint (death, MI, heart failure, or malignant ventricular arrhythmia) occurred in nearly 0.8% vs. 1.1%. Serious adverse events were similar between groups.
The trial excluded patients with clinical heart failure or other established indications for beta-blocker therapy, focusing on the population where contemporary evidence was most needed. Among patients with MI and LVEF of 40% or higher, beta-blocker therapy was associated with a lower risk of death or MACE compared with no therapy. The pragmatic design—registry-based follow-up and physician discretion in beta-blocker selection/dosing—supports generalizability to real-world practice.
Author disclosure forms are available at NEJM.org
Source: NEJM
