Beta-blocker therapy after myocardial infarction (MI) failed to lower the rate of all-cause death, MI, or heart failure in patients with a left ventricular ejection fraction (LVEF) of at least 50%, according to results of a meta-analysis of five randomized trials.

The findings were presented at the American Heart Association (AHA) Scientific Sessions 2025 and published in The New England Journal of Medicine.

The impetus for the meta-analysis came as a result of observations made while working on the 2017 European Society of Cardiology Clinical Practice Guidelines on the Management of ST-Segment Elevation MI, study co-author Borja Ibáñez, MD, PhD, told Medscape Medical News.

“All available randomized trials had been conducted before the reperfusion era, before routine invasive management, before complete revascularization, and before the widespread use of dual antiplatelet therapy and statins,” said Ibáñez, professor of cardiology at the National Center for Cardiovascular Research in Madrid, Spain. “In those early trials from the 1980s, beta-blockers demonstrated benefit mainly through reductions in malignant arrhythmias and progression to heart failure. However, in modern practice…the incidence of malignant arrhythmias and heart failure in patients with preserved ejection fraction is very low.”

This change in incidence rates casts substantial doubt on whether beta-blockers remained necessary in patients with preserved LVEF, Ibáñez said.

A ‘Unique Collaborative Effort’

To help answer this clinical question, Ibáñez and colleagues conducted a meta-analysis that included 17,801 patients from five open-label, randomized trials: REBOOT (n = 7459), REDUCE-AMI (n = 4967), BETAMI (n = 2441), DANBLOCK (n = 2277), and CAPITAL-RCT (n = 657). In all five trials, investigators randomly assigned patients with recent MI, no other indications for beta-blocker therapy, and an LVEF of at least 50% to beta-blocker therapy or no beta-blocker therapy.

Ibáñez described the study as a “unique collaborative effort” involving research teams from Europe, Japan, and New Zealand. All of the researchers shared the same goal of combining high-quality randomized evidence into a definitive meta-analysis.

“Because all [five] trials were investigator-initiated and designed solely to answer a clinically important question, collaboration came naturally,” Ibáñez said. “The results across most trials were remarkably consistent, although a few — such as BETAMI and DANBLOCK — showed a small signal toward reduction in MI, making it even more important to synthesize all available data.”

Comparable Outcomes

For the meta-analysis, a composite of death from any cause, MI, or heart failure served as the primary outcome measure.

In all, 49.6% of patients received a beta-blocker, and 50.4% received no beta-blocker.

During a median follow-up of 3.6 years, the occurrence of a primary endpoint event was similar between the beta-blocker vs no beta-blocker arms (8.1% vs 8.3%; P = .54).

Moreover, analysis of the individual endpoints of the primary outcome revealed no significant differences between the beta-blocker and no beta-blocker arms for the following:

• Death from any cause (hazard ratio [HR], 1.04; 95% CI, 0.89-1.21)
• MI (HR, 0.89; 95% CI, 0.77-1.03)
• Heart failure (HR, 0.87; 95% CI, 0.64-1.19)

Sunil V. Rao, MD, professor of medicine at the NYU Grossman School of Medicine in New York City, who was not involved in the study, said these data indicate that in the contemporary era, the role of beta-blockers in patients with normal LVEF probably is limited.

This finding, however, “does not apply to patients who have other indications for beta-blockers like low ejection fraction, atrial fibrillation, or hypertension,” Rao said in an interview. “It also does not apply to the acute setting where a patient with acute MI is hypertensive and tachycardic, where beta-blockade is useful.”

Understanding the Mechanisms

Ibáñez said the rationale behind the results is embedded within the mechanisms by which beta-blockers offer benefit after MI: reduction of malignant arrhythmias, prevention of adverse ventricular remodeling, and antianginal effects.

“In patients with preserved ejection fraction (by definition with small scar size), the risk of malignant arrhythmias and the likelihood of adverse remodeling are both very low,” Ibáñez said. “Moreover, because patients are treated according to current standards — with complete revascularization — there is minimal need for the antianginal properties of beta-blockers. Consequently, it is not surprising that no clinically meaningful benefit was observed in this population in contemporary randomized trials.”

Impact on Post-MI Care

The findings probably will have a big influence on clinical practice, according to Rao.

“Patients who are post-MI are on multiple medications, and if we can start removing some that have little to no benefit, then that’s good for patients,” he said.

However, Rao stressed that any patient currently on a beta-blocker should discuss this with their cardiologist before making any changes.

“Importantly, beta-blockers in patients with reduced left ventricular ejection fraction are very beneficial, and this meta-analysis does not apply to them,” he said.

Ibáñez noted that opportunities to generate such a volume of randomized evidence in such a short period — and to provide a clear and definitive answer to a long-standing clinical question — are rare.

“This collaborative effort represents an important step forward in evidence-based post-MI care,” he said.

Ibáñez and Rao reported having no relevant financial relationships.

Brian Ellis is a freelance writer and editor who lives in Southwest Virginia.