Is there a role for beta blockers (Beta-Adrenergic Blocking Agents) in the treatment of Heart Failure with preserved Ejection Fraction (HFpEF)?

Beta Blockers in HFpEF: Limited Role Without Specific Comorbidities

Beta blockers are not recommended as disease-modifying therapy for HFpEF and should only be used when specific comorbid indications exist, such as atrial fibrillation with rapid ventricular response, post-myocardial infarction, or symptomatic coronary artery disease. 1

Why Beta Blockers Are Not First-Line in HFpEF

Your understanding is largely correct. The evidence base for beta blockers in HFpEF is fundamentally different from HFrEF:

• No mortality benefit demonstrated: The 2022 AHA/ACC/HFSA guidelines note that while ESC HF guidelines state there is no specific drug treatment for HFpEF, beta blockers lack proven efficacy for the primary HFpEF syndrome itself 2

• Pathophysiological concerns: Beta blockers reduce heart rate and can contribute to chronotropic incompetence, which is already a key contributor to exercise intolerance in HFpEF patients who rely on adequate heart rate response during exercise to maintain cardiac output 1

• May worsen exercise capacity: The ACC and AHA guidelines specifically warn that beta blockers may contribute to exercise intolerance in HFpEF patients due to limiting chronotropic response 1

When Beta Blockers ARE Indicated in HFpEF

Beta blockers should be reserved for patients with HFpEF who have specific comorbid conditions 1:

• Post-myocardial infarction 2
• Symptomatic angina or coronary artery disease 2, 1
• Atrial fibrillation requiring rate control (though alternatives may be preferable if adverse effects occur) 2, 1
• Hypertension requiring additional blood pressure control 2
• Tachycardia with heart rate >80 bpm 2

The Nuance: Widespread Use Despite Lack of Evidence

There is an important disconnect between guideline recommendations and clinical practice:

• High utilization in clinical trials: In major HFpEF trials, 72-87% of patients were on beta blockers as add-on therapy for comorbidities (I-PRESERVE: 72%, PARAGON: 80%, EMPEROR-PRESERVED: 87%) 2

• Real-world practice: The DELIVER trial showed 83% of HFpEF patients were taking beta blockers, primarily for comorbidity management 3

• No harm demonstrated: Recent analyses show beta blocker use was not associated with higher risk of worsening HF or cardiovascular death in HFpEF patients 3, 4

Evidence for Mid-Range EF (HFmrEF)

The picture differs slightly for patients with LVEF 40-49%:

• SENIORS trial: Nebivolol showed benefit in unselected HF patients, with no difference in outcomes between reduced and preserved EF in prespecified subgroup analysis 2

• Individual patient-level meta-analysis: Beta blockers improved LVEF, all-cause mortality, and cardiovascular mortality in patients with mid-range/mildly reduced EF (40-49%) in sinus rhythm, similar to HFrEF 2

What TO Use for HFpEF Instead

First-line disease-modifying therapy 1, 5:

• SGLT2 inhibitors (dapagliflozin or empagliflozin) - Class 2a recommendation with proven reduction in HF hospitalizations and cardiovascular mortality 2, 5

Additional options 5:

• Mineralocorticoid receptor antagonists (spironolactone) - particularly for LVEF closer to 45-50% 5
• Loop diuretics - for symptom management and congestion relief 5

Clinical Approach

If your HFpEF patient is already on a beta blocker 1:

• Assess whether there is a specific indication (prior MI, CAD, AF, hypertension)
• If no clear indication exists, monitor for signs of exercise intolerance
• Consider dose reduction or discontinuation if symptoms worsen
• Do not routinely discontinue if patient is stable and tolerating well 3

If initiating new therapy for HFpEF 1, 5:

• Start with SGLT2 inhibitor as disease-modifying therapy
• Reserve beta blockers only for patients with specific comorbid indications
• For hypertension control in HFpEF, prefer RAAS antagonists (ACEi, ARB, or ARNi) over beta blockers 2, 5

Common Pitfall to Avoid

Do not extrapolate HFrEF treatment algorithms to HFpEF - these are distinct syndromes with different pathophysiology and treatment responses 5. Beta blockers are guideline-directed medical therapy for HFrEF but not for HFpEF in the absence of other indications 2, 1.