Why are beta blockers not preferred in Heart Failure with preserved Ejection Fraction (HFpEF)?

Beta Blockers in Heart Failure with Preserved Ejection Fraction (HFpEF)

Beta blockers are not preferred in HFpEF primarily because they may contribute to chronotropic incompetence and exercise intolerance without providing significant mortality or morbidity benefits in this population. 1

Pathophysiological Considerations

• Beta blockers reduce heart rate, which can be detrimental in HFpEF patients who rely on adequate chronotropic response during exercise to maintain cardiac output 1
• Unlike in HFrEF, where beta blockers have proven mortality benefits, their use in HFpEF lacks strong evidence for improving clinical outcomes 2, 3
• Chronotropic incompetence (inability to increase heart rate appropriately during exertion) is a key contributor to exercise intolerance in HFpEF patients 1

Evidence from Clinical Guidelines and Research

• The 2022 AHA/ACC/HFSA guidelines specifically note that beta blockers may contribute to exercise intolerance in HFpEF patients due to chronotropic incompetence 1
• Beta blockers are only recommended in HFpEF patients when there are specific comorbid indications such as:
  • History of myocardial infarction 1
  • Symptomatic coronary artery disease 1
  • Atrial fibrillation with rapid ventricular response 1, 4
• The RATE-AF trial in elderly patients with atrial fibrillation and symptoms of heart failure (mostly with preserved LVEF) found that beta blockers were associated with more adverse events (dizziness, lethargy, hypotension) compared to digoxin 1

Preferred Treatments for HFpEF

• SGLT2 inhibitors are now recommended as first-line disease-modifying therapy for HFpEF based on the EMPEROR-Preserved trial, which showed a 21% reduction in the primary composite endpoint of heart failure hospitalization or cardiovascular death 1, 2
• The DELIVER trial demonstrated that dapagliflozin significantly reduced heart failure hospitalizations and composite cardiovascular outcomes in HFpEF patients 2
• Other treatment options with better evidence in HFpEF include:
  • Mineralocorticoid receptor antagonists (MRAs) like spironolactone, particularly for patients with LVEF in the lower range of preservation (40-50%) 1, 2
  • RAAS antagonists including ACEi, ARB, and possibly ARNi as first-line agents for hypertension management in HFpEF 1

Recent Research Findings

• A 2019 secondary analysis of the TOPCAT trial found that beta blocker use was associated with a higher risk of HF hospitalization among patients with HFpEF with an EF of 50% or greater (hazard ratio, 1.74; 95% CI, 1.28-2.37) 5
• However, a 2024 analysis from the DELIVER trial found that beta blocker use was not associated with a higher risk of worsening HF or cardiovascular death in HFpEF patients 6
• The SwedeHF Registry study (2021) showed that in patients with HFpEF, beta blocker use was not associated with changes in HF hospitalization or cardiovascular mortality 7

Clinical Implications and Approach

• Focus on treatments with proven benefits in HFpEF, such as SGLT2 inhibitors, rather than beta blockers 2
• Reserve beta blockers for HFpEF patients with specific indications (post-MI, symptomatic CAD, or AF with rapid ventricular response) 1
• When beta blockers are necessary for comorbidity management in HFpEF patients, monitor for signs of exercise intolerance and consider dose adjustment if symptoms worsen 1, 4
• For HFpEF patients with atrial fibrillation, consider alternatives to beta blockers for rate control if patients experience adverse effects 1

Common Pitfalls to Avoid

• Applying HFrEF treatment paradigms to HFpEF patients without evidence 2
• Overlooking the potential negative impact of beta blockers on exercise capacity in HFpEF patients 1
• Failing to prioritize therapies with proven benefits in HFpEF (SGLT2 inhibitors, MRAs) over those with uncertain benefits 2