How do I switch from Valsartan (Angiotensin II Receptor Blocker) to an Angiotensin Receptor-Neprilysin Inhibitor (ARNI) like Sacubitril/Valsartan?

Switching from Valsartan to ARNI (Sacubitril/Valsartan)

When switching from valsartan (an ARB) to sacubitril/valsartan, you can make the switch immediately without any washout period, unlike when switching from an ACE inhibitor which requires a 36-hour washout. 1

Key Difference: No Washout Required from ARBs

• The critical 36-hour washout period is ONLY required when switching from an ACE inhibitor to ARNI, not from an ARB like valsartan. 1
• This is because the risk of angioedema is specifically elevated when combining neprilysin inhibition with ACE inhibition, not with ARB therapy. 1
• You can stop valsartan and start sacubitril/valsartan the same day or next day. 1

Initial Dosing Based on Current Valsartan Dose

High-dose ARB (valsartan ≥160 mg total daily): 1

• Start sacubitril/valsartan at 49/51 mg twice daily
• This is the standard starting dose for patients on adequate ARB therapy

Low- or medium-dose ARB (valsartan <160 mg total daily): 1

• Start sacubitril/valsartan at 24/26 mg twice daily
• This lower starting dose allows for safer titration in patients not on high-dose ARB therapy

Dose Titration Schedule

• Double the dose every 2-4 weeks as tolerated by the patient 1, 2
• Target maintenance dose is 97/103 mg twice daily 1
• Both gradual (6 weeks) and condensed (3 weeks) titration approaches are similarly tolerated, but gradual titration maximizes achievement of target dose in patients previously on low-dose ACEi/ARB 1

Special Populations Requiring Lower Starting Dose (24/26 mg twice daily)

Start at 24/26 mg twice daily in: 1, 2

• Severe renal impairment (eGFR <30 mL/min/1.73 m²)
• Moderate hepatic impairment (Child-Pugh Class B)
• Elderly patients (age ≥75 years)
• Systolic blood pressure <100 mmHg
• Volume-depleted patients

Note: Mild-to-moderate renal impairment (eGFR 30-59 mL/min/1.73 m²) requires no starting dose adjustment 1

Critical Monitoring After Switch

Within 1-2 weeks after initiation or dose increase, check: 3

• Blood pressure (watch for symptomatic hypotension)
• Serum creatinine and eGFR
• Serum potassium

Red flags requiring dose reduction: 3

• Decrease in eGFR >30% from baseline
• Development of hyperkalemia
• Symptomatic hypotension

Managing Hypotension During Transition

• Sacubitril/valsartan exerts a more pronounced blood pressure-lowering effect compared to ARBs alone 1
• In non-congested patients with borderline blood pressure (systolic ≤100 mmHg), empirically reduce loop diuretic dose modestly to mitigate hypotensive effects 1
• Ensure patients are not volume-depleted at time of initiation 1
• Up to 25% of patients may develop hypotension, but this is manageable with careful monitoring 1, 4

Absolute Contraindications to Check Before Switching

Do not initiate sacubitril/valsartan if: 1, 5

• History of angioedema (with or without prior ACEi/ARB use)
• Currently taking an ACE inhibitor (or within 36 hours of last ACEi dose)
• Pregnancy or lactation
• Severe hepatic impairment (Child-Pugh C)
• Concomitant aliskiren use in patients with diabetes
• Known hypersensitivity to ARBs or ARNIs

Clinical Benefits Supporting This Switch

• The 2022 AHA/ACC/HFSA guidelines give a Class 1, Level B-R recommendation for replacing an ARB with ARNI in patients with chronic symptomatic HFrEF NYHA class II or III to further reduce morbidity and mortality 1
• PARADIGM-HF demonstrated 20% relative reduction in cardiovascular death or HF hospitalization compared to enalapril 1
• This benefit extends across the spectrum of patients, including those switching from ARBs 1