Beta-Blocker Therapy Fails to Improve Major Outcomes After MI with Normal Ejection Fraction: NEJM Evidence

In a recent meta-analysis which included individual-patient data from five randomized trials, beta-blocker therapy did not decrease the incidence of death from any cause, myocardial infarction (MI), or heart failure (HF) in patients with a left ventricular ejection fraction (LVEF) of at least 50% after MI without other indications for beta-blockers.

These pivotal findings were published in November 2025, in the New England Journal of Medicine- Evidence.

Reflecting Upon Applicability of Beta Blockers through Cardiovascular Management Landscape

Beta-blockers have traditionally been standard therapy after MI, based on trials from the early 1980s. However, advances in diagnostics, reperfusion, revascularization, and contemporary pharmacotherapy have improved outcomes, raising questions about their continued routine use in patients without heart failure or reduced LVEF (<40%). Guideline recommendations now differ; The European Society of Cardiology (ESC) gives a Class IIa recommendation for patients with preserved LVEF, while American Heart Association and American College of Cardiology (AHA/ACC) guidelines continue to assign a Class I recommendation for all MI patients. Five recent randomized trials in patients with preserved LVEF have reported mixed findings, and none were individually powered to evaluate major outcomes. This meta-analysis pooled individual-patient data from these trials to more definitively assess the impact of beta-blockers on morbidity and mortality after MI in patients with LVEF ≥50%.

Study Overview

This was a preplanned, individual-patient level meta-analysis pooling data from five investigator-initiated, open-label, randomized, superiority trials: REBOOT, REDUCE-AMI, BETAMI, DANBLOCK, and CAPITAL-RCT*. The trials specifically included patients with a recent MI (within 14 days before randomization) and a preserved LVEF (at least 50%). Patients were randomized to receive oral beta-blocker therapy or no beta-blocker therapy. Importantly, patients with any other indication for beta-blockers (such as heart failure) or any contraindication were excluded.

The meta-analysis included a large cohort of 17,801 patients.

The prespecified primary end point was a composite of death from any cause, myocardial infarction, or heart failure.

Key Findings

During a median follow-up of 3.6 years, a primary-end-point event occurred in 8.1% (717 patients) in the beta-blocker group and 8.3% (748 patients) in the no-beta-blocker group.

Treatment with beta-blockers did not significantly reduce the incidence of the composite primary endpoint. Analysis of individual components similarly showed no meaningful benefit:

• All-cause mortality: 1.07 events per 100 patient-years in the beta-blocker group vs 1.03 events per 100 patient-years in the no–beta-blocker group

• Myocardial infarction: 1.19 events per 100 patient-years in the beta-blocker group vs 1.33 events per 100 patient-years in the no–beta-blocker group

• Heart failure: 0.24 events per 100 patient-years in the beta-blocker group vs 0.28 events per 100 patient-years in the no–beta-blocker group

Safety endpoints, including advanced atrioventricular block and ischemic stroke, were also consistent between the groups. The results were generally consistent across all prespecified subgroups, including women and older patients.

Implications for Practice

This comprehensive meta-analysis strongly suggests that the widespread practice of prescribing beta-blockers universally to all post-MI patients, regardless of LVEF, requires re-evaluation. For patients with a preserved LVEF (at least 50%) and no compelling alternative indications, beta-blocker therapy did not provide a measurable reduction in the risk of subsequent death, MI, or heart failure.

The lack of effect in this population is likely due to their favorable baseline prognosis. Patients with preserved LVEF typically have less myocardial scarring and fewer co-existing diseases compared to those with reduced LVEF, making them less vulnerable to the ventricular arrhythmias that beta-blockers typically mitigate.

Clinicians should note that this finding does not negate the benefit of beta-blockers for patients who have reduced LVEF (<40%) or who have established indications for the drug, such as uncontrolled hypertension, atrial fibrillation or heart failure. However, for the specific cohort of patients with preserved LVEF without other established indications, this pooled evidence supports revisiting consideration of blanket beta-blocker prescription.

Abbreviations: *REBOOT (Treatment with Beta-Blockers after Myocardial Infarction without Reduced Ejection Fraction), REDUCE-AMI (Randomized Evaluation of Decreased Usage of Beta-Blockers after Acute Myocardial Infarction), 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), and CAPITAL-RCT (Carvedilol Post Intervention Long-Term Administration in Large Scale Randomized Controlled Trial)

Reference: Kristensen AM, Rossello X, Atar D, Yndigegn T, Kimura T, Latini R, Lindahl B, Halvorsen S, Olsen MH, Fuster V, Hofmann R. Beta-Blockers after Myocardial Infarction with Normal Ejection Fraction. New England Journal of Medicine. 2025 Nov 9.

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