Are Angiotensin-Converting Enzyme (ACE) inhibitors and beta blockers effective for heart failure with preserved ejection fraction?

ACE Inhibitors and Beta Blockers in Heart Failure with Preserved Ejection Fraction

Beta blockers and ACE inhibitors are not specifically recommended as primary treatments for heart failure with preserved ejection fraction (HFpEF), but SGLT2 inhibitors have stronger evidence for reducing hospitalizations and cardiovascular mortality in this population.

Current Evidence for HFpEF Treatment

SGLT2 Inhibitors - First Line Therapy

• SGLT2 inhibitors have a Class 2a recommendation (moderate strength) for HFpEF treatment based on recent guidelines, as they can decrease heart failure hospitalizations and cardiovascular mortality 1
• In the EMPEROR-PRESERVED trial, 86-87% of participants were already taking beta-blockers at baseline, indicating common use in clinical practice 1

Beta Blockers in HFpEF

• There is insufficient evidence to recommend beta blockers specifically for HFpEF treatment 1, 2
• However, beta blockers are frequently used in HFpEF patients in clinical trials:
  • 72% of patients in I-PRESERVE trial 1
  • 80% in PARAGON trial 1
  • 87% in EMPEROR-PRESERVED trial 1
• Beta blockers may be beneficial in specific HFpEF patients who have:
  • Coronary artery disease 1
  • Atrial fibrillation requiring rate control 1
  • Hypertension 1
  • Tachycardia 1

ACE Inhibitors and ARBs in HFpEF

• ACE inhibitors do not have strong evidence supporting their use specifically for HFpEF 1, 3, 4
• ARBs have a weak recommendation (Class 2b) for selected HFpEF patients, particularly those with LVEF on the lower end of the preserved spectrum 1
• In major HFpEF trials, ACE inhibitor/ARB use varied:
  • PEP-CHF: 55% on ACE inhibitors 1
  • CHARM-PRESERVED: 56% on ARBs 1
  • I-PRESERVE: 58% on ARBs 1

Treatment Algorithm for HFpEF

1. First-line therapy:

   • SGLT2 inhibitors (Class 2a recommendation) 1
   • Diuretics as needed for symptom management 1

2. Second-line options (Class 2b recommendations):

   • Mineralocorticoid receptor antagonists (MRAs) 1, 4
   • ARBs 1, 4
   • ARNi (angiotensin receptor-neprilysin inhibitor) 1

3. Additional treatments based on comorbidities:

   • Treat hypertension aggressively (Class 1 recommendation) 1
   • Manage atrial fibrillation appropriately (Class 2a recommendation) 1
   • Beta blockers if indicated for comorbidities like coronary artery disease, tachycardia, or atrial fibrillation 1, 5

Important Clinical Considerations

• HFpEF treatment differs significantly from HFrEF treatment, where ACE inhibitors and beta blockers are cornerstones of therapy 2, 6
• Avoid routine use of nitrates or phosphodiesterase-5 inhibitors in HFpEF as they are ineffective (Class 3: No Benefit) 1
• The evidence for beta blockers in HFpEF remains controversial, with potential benefits in specific phenotypes but limited evidence for routine use 5, 4
• For patients with HFmrEF (EF 41-49%), SGLT2i have stronger evidence (Class 2a), while beta blockers, ACEi, ARBs, ARNi, and MRAs have weaker evidence (Class 2b) 1

Pitfalls to Avoid

• Do not automatically apply HFrEF treatment algorithms to HFpEF patients, as the pathophysiology and evidence base differ significantly 1, 2
• Monitor for hyperkalaemia when using MRAs or ARBs in HFpEF patients, as this is a common adverse effect 4
• Recognize that many HFpEF patients receive beta blockers in clinical practice despite limited evidence, often due to comorbidities rather than for HFpEF itself 1
• Do not discontinue beta blockers or ACE inhibitors if they are indicated for other conditions (e.g., post-MI, hypertension) 1