What is the role of beta (beta blockers) blockers, such as metoprolol (metoprolol) or carvedilol (carvedilol), in patients with normal Ejection Fraction (EF)?

Beta-Blockers in Patients with Normal Ejection Fraction: Current Evidence

In patients with chronic coronary disease and normal ejection fraction (≥50%) without prior myocardial infarction, beta-blockers are not beneficial for reducing major adverse cardiovascular events and should not be routinely prescribed for this indication alone. 1

Current Guideline Recommendations

The 2023 ACC/AHA guidelines represent a significant shift from previous recommendations:

• Class III (No Benefit): Beta-blockers should NOT be used in patients with chronic coronary disease without prior MI or LVEF ≥50%, in the absence of another primary indication (angina, arrhythmias, or uncontrolled hypertension). 1

• Class IIb (May Be Reasonable): For patients who were started on beta-blockers after MI but now have normal EF (>50%) and no ongoing angina, arrhythmias, or uncontrolled hypertension, it may be reasonable to reassess and potentially discontinue beta-blocker therapy after >1 year. 1

This contrasts sharply with older 2011 guidelines that recommended beta-blockers for 3 years post-MI in all patients with normal LV function (Class I recommendation). 1

When Beta-Blockers ARE Indicated in Normal EF

Beta-blockers remain essential in specific clinical scenarios:

• Reduced ejection fraction (<40-50%): Class I recommendation for carvedilol, metoprolol succinate, or bisoprolol to reduce mortality and MACE. 1

• Post-MI with reduced EF: Mandatory therapy regardless of symptoms. 1

• Symptomatic angina: Beta-blockers remain first-line for symptom control. 1

• Atrial fibrillation rate control: Beta-blockers are the most effective drug class for rate control, achieving target heart rates in 70% of patients. 1

• Uncontrolled hypertension: When beta-blockers are needed as part of antihypertensive regimen. 1

Evidence Supporting the Paradigm Shift

The downgrading of beta-blocker recommendations in normal EF patients reflects:

• Lack of mortality benefit: Studies consistently fail to demonstrate survival advantage in chronic coronary disease patients with preserved EF without recent MI. 1

• No reduction in MACE: Beta-blockers do not reduce major adverse cardiovascular events in this population. 1

• Modern revascularization era: Historical trials predated contemporary PCI and optimal medical therapy with statins, ACE inhibitors, and antiplatelet agents. 1

Heart Failure with Preserved Ejection Fraction (HFpEF)

Beta-blockers show potential harm in HFpEF, particularly when EF >60%:

• Propensity-matched analysis of 435,897 patients showed beta-blockers were associated with higher risk of HF hospitalization as EF increased, with particular concern when EF >60%. 2

• Beta-blockers may be beneficial in HFmrEF (EF 40-49%) but lack established benefit in HFpEF (EF ≥50%). 2, 3

• The available evidence for beta-blockers in HFpEF is limited and does not support routine use absent alternative indications. 3

Specific Beta-Blocker Selection When Indicated

When beta-blockers ARE indicated for reduced EF:

• Only three agents have proven mortality benefit: carvedilol, metoprolol succinate (extended-release), and bisoprolol. 1, 4

• Target doses matter: Metoprolol succinate 200 mg daily, carvedilol 25 mg twice daily, or bisoprolol to target doses. 1, 4

• Carvedilol vs metoprolol succinate: Meta-analyses show similar mortality reduction between these agents in HFrEF, though some observational data suggest potential carvedilol superiority over metoprolol tartrate. 5, 6

Common Pitfalls to Avoid

• Continuing beta-blockers indefinitely post-MI in normal EF patients: The 2023 guidelines support reassessment after 1 year if EF remains >50% and no other indications exist. 1

• Using non-evidence-based beta-blockers: Metoprolol tartrate (immediate-release), atenolol, and other agents lack mortality data in heart failure. 1, 4

• Prescribing beta-blockers for "stable CAD" with normal EF: This is now a Class III (no benefit) recommendation. 1

• Underdosing when indicated: When beta-blockers ARE appropriate (reduced EF), achieving target doses is critical for mortality benefit. 4

Practical Algorithm for Decision-Making

Step 1: Determine current LVEF

• If LVEF <50%: Beta-blocker indicated (Class I) 1
• If LVEF ≥50%: Proceed to Step 2

Step 2: Assess for alternative indications

• Symptomatic angina? → Beta-blocker indicated 1
• Atrial fibrillation requiring rate control? → Beta-blocker indicated 1
• Uncontrolled hypertension? → Consider beta-blocker 1
• None of above? → Proceed to Step 3

Step 3: History of recent MI?

• MI within past year with normal EF: Consider continuing beta-blocker 1
• MI >1 year ago with persistently normal EF: Reassess need and consider discontinuation 1
• No MI history: Do not initiate beta-blocker (Class III) 1