Is it better to treat recovered ejection fraction (EF) with Angiotensin-Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARBs)?

Treatment of Recovered Ejection Fraction: ACE Inhibitors vs ARBs

ACE inhibitors should be used as first-line therapy for patients with recovered ejection fraction, with ARBs reserved as an alternative for patients who cannot tolerate ACE inhibitors due to side effects such as cough or angioedema. 1

Evidence-Based Rationale

Efficacy Comparison

• ACE inhibitors have more robust evidence supporting their use in heart failure patients, including those with recovered EF
• Both ACE inhibitors and ARBs provide similar benefits in terms of mortality reduction (5-16% risk reduction with ACE inhibitors) 1
• ACE inhibitors are considered essential treatments for patients with heart failure and reduced ejection fraction, with ARBs being a reasonable alternative when ACE inhibitors cannot be tolerated 1

Side Effect Profile

• ACE inhibitors are associated with cough in approximately 5-10% of white patients and up to 50% in Chinese patients 1
• Angioedema occurs in <1% of patients taking ACE inhibitors but is more frequent in Black patients 1, 2
• ARBs have a better tolerability profile with fewer side effects like cough 2, 3
• Both medication classes carry similar risks of hypotension, renal dysfunction, and hyperkalemia 2

Algorithm for Treatment Decision

1. First-line therapy: Start with an ACE inhibitor at the recommended starting dose

   • Examples: Enalapril 2.5 mg twice daily, Lisinopril 2.5-5 mg daily, Ramipril 1.25-2.5 mg once daily 1
   • Titrate to target doses as tolerated (Enalapril 10-20 mg twice daily, Lisinopril 20-40 mg daily) 1

2. Monitor for side effects:

   • Persistent dry cough
   • Angioedema (facial/tongue swelling)
   • Hypotension, hyperkalemia, or worsening renal function

3. Switch to ARB if:

   • Patient develops persistent and troublesome cough that resolves after ACE inhibitor discontinuation 1
   • Patient experiences angioedema (absolute contraindication to further ACE inhibitor use) 1
   • Recommended ARBs: Candesartan 4-8 mg daily (target 32 mg), Valsartan 40 mg twice daily (target 160 mg twice daily) 1

4. No washout period required when switching from ACE inhibitor to ARB 2

   • Monitor blood pressure, renal function, and potassium within 1-2 weeks after switching

Important Clinical Considerations

• ARBs should not be combined with ACE inhibitors due to increased risk of adverse effects without additional mortality benefit 2, 3, 4
• Patients with recovered EF should continue to receive evidence-based therapy that was effective during the reduced EF phase
• Target doses should be achieved whenever possible, as outcomes are better with higher doses 5
• Special caution is needed when using either medication class in patients with:
  • Low systolic blood pressure (<80 mmHg)
  • Impaired renal function
  • Elevated serum potassium
  • Volume depletion 2

Monitoring Recommendations

• Blood pressure, renal function, and serum potassium should be checked within 1-2 weeks after initiation or dose changes 2
• More frequent monitoring may be needed in patients with renal impairment or those taking other medications that affect potassium levels (e.g., potassium-sparing diuretics) 6
• Avoid NSAIDs when possible as they may reduce the effectiveness of both ACE inhibitors and ARBs 6

By following this approach, clinicians can optimize therapy for patients with recovered ejection fraction while minimizing adverse effects and maximizing clinical benefits.