When to switch from Angiotensin Receptor Blocker (ARB) to Angiotensin Receptor-Neprilysin Inhibitor (ARNI), such as sacubitril/valsartan, in patients with chronic heart failure?

When to Switch from ARB to ARNI in Chronic Heart Failure

Patients with heart failure with reduced ejection fraction (HFrEF) who have LVEF ≤40% and remain symptomatic (NYHA class II-III) despite at least 3 months of ACE inhibitor or ARB therapy should be switched to an ARNI (sacubitril/valsartan) to reduce morbidity and mortality. 1

Patient Selection Criteria for ARB to ARNI Switch

Required Criteria:

• LVEF ≤40% (current or prior) 1
• Symptomatic heart failure (NYHA class II-III) despite optimal medical therapy 1
• At least 3 months of prior ACE inhibitor or ARB therapy 1
• Stable clinical condition (not currently decompensated) 1

Contraindications:

• History of angioedema 1
• Systolic blood pressure <100 mmHg 1
• Severe renal impairment (eGFR <30 mL/min/1.73m²) 1
• Current pregnancy or planning pregnancy 2

Switching Protocol

1. For patients on ARB:

   • No washout period required
   • Can initiate ARNI immediately after the last ARB dose 2

2. For patients on ACE inhibitor:

   • Mandatory 36-hour washout period after the last ACE inhibitor dose 2
   • Failure to observe this washout period increases risk of angioedema 2

3. Initial ARNI dosing:

   • Standard starting dose: 49/51 mg twice daily for most patients
   • Lower starting dose for patients with:
     • Severe renal impairment
     • Moderate hepatic impairment 2

4. Titration:

   • Target dose: 97/103 mg twice daily
   • Titrate every 2-4 weeks as tolerated 2

Clinical Benefits of Switching

The PARADIGM-HF trial demonstrated that switching from ACE inhibitor/ARB to ARNI provides:

• 20% reduction in cardiovascular death or HF hospitalization 1
• Number needed to treat: 21 patients over 27 months to prevent one primary endpoint 1
• 20% reduction in sudden cardiac death 1
• Significant improvements in:
  • Left ventricular function (median LVEF increase from 28.2% to 37.8%) 1
  • Ventricular remodeling 1
  • Quality of life 1

Monitoring After Switch

• Blood pressure (watch for symptomatic hypotension, more common than with ACE inhibitors) 1, 2
• Renal function 2
• Electrolytes, particularly potassium 2

Common Pitfalls to Avoid

1. Failure to recognize eligible patients:

   • Up to 38% of HFrEF patients may be eligible for ARNI therapy 3
   • Delaying ARNI initiation can result in suboptimal outcomes 2

2. Medication errors:

   • Concurrent use of ACE inhibitor with ARNI (increases angioedema risk) 2
   • Inadequate washout period when switching from ACE inhibitor 2

3. Inadequate monitoring:

   • Failure to monitor for hypotension (most common side effect) 1, 2
   • Inadequate follow-up of renal function and electrolytes 2

4. Suboptimal dosing:

   • Failure to titrate to target dose when tolerated 1

By following these guidelines for switching from ARB to ARNI in appropriate patients with chronic heart failure, clinicians can significantly improve outcomes including mortality, hospitalization rates, and quality of life.