Switching from ARB to Sacubitril/Valsartan in HFrEF
Switch any symptomatic HFrEF patient currently on an ARB to sacubitril/valsartan immediately, as this replacement reduces cardiovascular death and heart failure hospitalization regardless of symptom severity. 1
When to Switch: Clinical Criteria
All HFrEF patients on ARBs are candidates for switching to sacubitril/valsartan - you do not need to wait for patients to "fail" optimal medical therapy first. 1 The evidence supports:
- LVEF ≤40% (or ≤35% based on stricter criteria) 2
- Any NYHA class II-IV symptoms - even mild symptoms warrant switching 1
- Stable clinical status - not actively decompensated 1
- Systolic BP ≥100 mm Hg preferred, though lower BP is not an absolute contraindication 1
Key Advantage: No Washout Period Required
When switching from an ARB to sacubitril/valsartan, you can make the switch immediately without any washout period. 3 This is a critical practical advantage over switching from ACE inhibitors, which require a mandatory 36-hour washout to avoid angioedema. 1, 2
How to Switch: Practical Algorithm
Step 1: Verify No Contraindications 1, 2
- History of angioedema (absolute contraindication)
- Pregnancy or lactation
- Severe hepatic impairment (Child-Pugh C)
- Concomitant ACE inhibitor use (must be stopped ≥36 hours prior)
Step 2: Determine Starting Dose 1, 3
Standard patients: Start 49/51 mg twice daily 1, 3
High-risk patients (start 24/26 mg twice daily): 1, 3
- Age ≥75 years
- Severe renal impairment (eGFR <30 mL/min/1.73 m²)
- Moderate hepatic impairment (Child-Pugh B)
- Systolic BP 90-100 mm Hg
Step 3: Make the Switch
- Stop the ARB and start sacubitril/valsartan the same day - no waiting period needed 3
- Consider reducing loop diuretic dose by 25-50% in non-congested patients to prevent hypotension 1, 3
Step 4: Titration Schedule 3
- Double the dose every 2-4 weeks as tolerated
- Target dose: 97/103 mg twice daily 3
- Monitor BP, renal function, and potassium within 1-2 weeks after each dose change 3
Managing Common Barriers
Hypotension (Most Common Issue) 1, 3
- Asymptomatic hypotension is NOT a reason to avoid switching - sacubitril/valsartan provides mortality benefit even with lower BP 3
- If symptomatic hypotension occurs:
Elevated Potassium 4
- Sacubitril/valsartan may actually lower potassium levels compared to ARBs alone 4
- In patients with baseline elevated K+, levels decreased by 0.5 mmol/L post-initiation 4
Renal Function Changes 1
- Mild creatinine elevation (<0.5 mg/dL increase) is acceptable and does not require dose adjustment 1
- Severe renal impairment requires starting at 24/26 mg twice daily but is not a contraindication 1, 2
Treatment Sequence Context
The European Society of Cardiology treatment algorithm positions sacubitril/valsartan as: 3
- First-line: ACE inhibitor + beta-blocker + SGLT2 inhibitor
- Second-line: Add mineralocorticoid receptor antagonist if symptomatic
- Third-line: Replace ACE inhibitor/ARB with sacubitril/valsartan if still symptomatic
However, recent evidence supports direct-to-ARNI initiation without requiring prior ACE inhibitor/ARB exposure, suggesting the traditional stepwise approach may be unnecessarily conservative. 1
Evidence Base
The PARADIGM-HF trial demonstrated sacubitril/valsartan reduced the composite endpoint of cardiovascular death or HF hospitalization by 20% (absolute risk reduction 4.7%, NNT=21 over 27 months) compared to enalapril. 1 Meta-analysis of 48 trials with 19,086 participants confirmed mortality benefit (RR 0.86,95% CI 0.79-0.94) and reduced serious adverse events (RR 0.89,95% CI 0.86-0.93). 5
The benefit applies broadly - not just to the narrow PARADIGM-HF population - across age, sex, etiology, comorbidities, and baseline EF. 5, 6
Critical Pitfall to Avoid
Do not fail to switch due to asymptomatic hypotension or minor laboratory changes. 3 The mortality benefit of sacubitril/valsartan persists even with lower blood pressures, and temporary dose adjustments with subsequent re-titration are preferable to avoiding the switch entirely. 3