How long should a patient wait after stopping Angiotensin Receptor Blocker (ARB) before starting Angiotensin Receptor-Neprilysin Inhibitor (ARNi)?

Timing of ARNi Initiation After Stopping ARB

When switching from an ARB to an ARNi, no washout period is required, and the ARNi can be initiated immediately after the last ARB dose. 1

Evidence-Based Recommendations

The 2022 AHA/ACC/HFSA guidelines for heart failure management provide clear direction on the timing of ARNi initiation after discontinuing renin-angiotensin system inhibitors:

• For ACE inhibitors: A mandatory 36-hour washout period is required before starting an ARNi 1, 2
• For ARBs: No washout period is required; ARNi can be started immediately after the last ARB dose 1

Rationale for Different Washout Requirements

Why ACE inhibitors require a washout period:

• The combination of neprilysin inhibition with ACE inhibition can lead to excessive bradykinin accumulation
• This significantly increases the risk of angioedema, which can be life-threatening 1
• Historical evidence from omapatrilat (combined ACE/neprilysin inhibitor) showed unacceptable rates of angioedema 1

Why ARBs do not require a washout period:

• ARBs do not affect bradykinin metabolism in the same way as ACE inhibitors
• The risk of angioedema when transitioning directly from ARB to ARNi is not elevated
• The ARB component in ARNi (valsartan) works through the same mechanism as the patient's previous ARB

Practical Implementation

When transitioning from an ARB to sacubitril/valsartan (ARNi):

1. Discontinue the ARB
2. Start ARNi with the next scheduled dose (no waiting period required)
3. Initial dosing:
   • For most patients: Start with 49/51 mg twice daily 3
   • For patients with severe renal impairment (eGFR <30 mL/min/1.73 m²): Start with 24/26 mg twice daily 3
   • For patients with moderate hepatic impairment: Start with 24/26 mg twice daily 3
4. Titration: Increase dose every 2-4 weeks to target dose of 97/103 mg twice daily as tolerated 3

Monitoring Recommendations

• Check blood pressure, electrolytes, and renal function after initiation and during titration 3
• Consider checking electrolytes and renal function 2-3 days after initiation 3
• Monitor for potential adverse effects including hypotension, renal dysfunction, and hyperkalemia 3

Important Cautions

• Never administer ARNi to patients with any history of angioedema 1
• Never administer ARNi concomitantly with an ACE inhibitor 1, 2
• Ensure proper patient education about the importance of not taking ACE inhibitors while on ARNi therapy 2

By following these guidelines, clinicians can safely transition patients from ARB therapy to ARNi therapy to improve morbidity and mortality outcomes in appropriate heart failure patients.