What is the role of beta blockers (beta-adrenergic blocking agents) in patients post-acute myocardial infarction (AMI) with preserved left ventricular ejection fraction (LVEF)?

Beta Blockers Post-AMI with Preserved LVEF: Current Evidence Summary

The evidence for routine beta-blocker use in post-AMI patients with preserved LVEF (>40%) is uncertain and currently under investigation, with no large randomized controlled trials supporting their use in this specific population. 1

Key Evidence Gaps

The most recent 2024 ESC Guidelines for Chronic Coronary Syndromes explicitly acknowledge that there are no large RCTs supporting the prescription of beta-blockers after uncomplicated ACS in patients with LVEF >40%, despite solid evidence existing for patients with reduced LVEF. 1

Historical Context vs. Modern Practice

• Most beta-blocker trials demonstrating mortality benefit were conducted in the pre-reperfusion era among patients with STEMI, often with reduced ejection fraction or heart failure complications 1
• The evidence base predates modern biomarker-based MI diagnosis, routine revascularization, and contemporary medical therapy 2
• Beta-blockers reduce mortality by 35% and specifically reduce sudden cardiac death in patients with reduced LVEF (≤35-40%), but this benefit is unproven in those with preserved LVEF 1

Current Guideline Recommendations

For Preserved LVEF Post-AMI

The 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guidelines recommend early (<24 hours) initiation of oral beta-blocker therapy in patients with ACS without contraindications to reduce reinfarction and ventricular arrhythmias. 1 However, this recommendation applies broadly to ACS patients and does not specifically address long-term use in those with preserved LVEF.

The 2024 ESC Guidelines recommend beta-blockers as initial treatment for symptom control in chronic coronary syndrome but note the clinical benefit beyond improving symptoms is largely unknown in patients with CAD without prior MI and normal LVEF. 1

For Reduced LVEF Post-AMI

• Class I recommendation for evidence-based beta blockers in all patients with recent or remote MI and reduced EF to prevent symptomatic heart failure and reduce mortality 1
• Specific beta blockers proven in heart failure with reduced ejection fraction include bisoprolol, carvedilol, and extended-release metoprolol succinate 1

Conflicting Observational Data

The 2024 ESC Guidelines note that observational studies and meta-analyses show conflicting results: 1

• Some suggest an association between beta-blockers and better clinical outcomes in preserved LVEF patients
• Others show a lack of association with mortality or cardiovascular events

Duration of Therapy Debate

The optimal duration of beta-blocker therapy in patients with prior MI and preserved LVEF remains controversial: 1

• One study suggested clinical benefit may be restricted to the first year after the index event, with discontinuation at 1 year not associated with higher 5-year mortality 1
• A Swedish study showed no association between beta-blocker use and composite outcomes (all-cause mortality, MI, unscheduled revascularization, or HF hospitalization) when follow-up started 1 year after ACS 1
• Another study found discontinuation beyond 1 year was associated with increased risk of death or readmission for ACS, but not all-cause mortality 1

Ongoing Clinical Trials

Three large-scale European pragmatic RCTs are currently underway to definitively answer whether beta-blockers benefit post-ACS patients with preserved LVEF: 1

• REDUCE-AMI trial (Sweden, Estonia, New Zealand): ~5000 patients with acute MI and EF ≥50% randomized to long-term beta-blockade or not, with primary endpoint of death or recurrent MI 2
• Two additional trials testing beta-blocker withdrawal at 6-12 months after uncomplicated ACS in patients with LVEF ≥40% (NCT03498066, NCT04769362) 1

Clinical Approach in Current Practice

Early Post-AMI Period

Initiate oral beta-blocker therapy within 24 hours in patients without contraindications (acute HF, cardiogenic shock, severe bradycardia, high-degree AV block, active bronchospasm) to reduce reinfarction and ventricular arrhythmias. 1

Long-Term Management

For patients with preserved LVEF (>40%) after uncomplicated MI:

• Beta-blockers are reasonable for symptom control if angina is present 1
• Beta-blockers are indicated if there are other compelling indications (hypertension, atrial fibrillation, heart failure) 1
• For patients without ongoing symptoms or other indications, the mortality benefit is unproven and continuation beyond 1 year is debatable pending ongoing trial results 1

Common Pitfalls to Avoid

• Do not assume the mortality benefit seen in reduced LVEF patients applies to those with preserved LVEF 1
• Reassess patients with initial contraindications after 24 hours, as many may become eligible for beta-blocker therapy 1
• Avoid nondihydropyridine calcium channel blockers (diltiazem, verapamil) in patients with low LVEF, as they may be harmful 1
• Do not routinely continue beta-blockers indefinitely in all post-MI patients with preserved LVEF without considering individual risk-benefit, as evidence from RCTs rarely extends beyond a few years 1