Indications for ARNI (Sacubitril/Valsartan)
Sacubitril/valsartan is indicated for adult patients with chronic heart failure and reduced ejection fraction (LVEF ≤40%) who remain symptomatic despite optimal medical therapy, and can be initiated in hospitalized patients with acute decompensated heart failure after hemodynamic stabilization. 1, 2
Primary Indication: Chronic Heart Failure with Reduced Ejection Fraction
Adult patients with HFrEF (LVEF ≤40%) and NYHA class II or III symptoms who tolerate an ACE inhibitor or ARB should be switched to sacubitril/valsartan to reduce cardiovascular death and heart failure hospitalization by 20%. 1
Specific Patient Criteria:
- Age ≥18 years with current or prior LVEF ≤40% 1
- Symptomatic heart failure (NYHA class II-III) despite at least 3 months of ACE inhibitor or ARB therapy 1
- Ability to tolerate ACE inhibitor or ARB without angioedema 1
- The medication reduces both cardiovascular death and heart failure hospitalization to a similar extent, with consistent benefits across all patient subgroups 1
Secondary Indication: Acute Decompensated Heart Failure
Sacubitril/valsartan can be initiated in hospitalized patients with acute decompensated HFrEF before discharge, after achieving hemodynamic stabilization. 1, 3
Requirements for In-Hospital Initiation:
- Resolution of acute pulmonary congestion 4
- Hemodynamic stability achieved 3
- Systolic blood pressure maintained >100 mmHg during the 6 hours prior to initiation 4
- This approach improves health status, reduces NT-proBNP by 46.7% (vs. 25.3% with enalapril), and improves left ventricular remodeling without increased adverse events 1, 3
De Novo Initiation (Without Prior ACE Inhibitor/ARB)
Sacubitril/valsartan may be initiated de novo in patients with symptomatic chronic HFrEF to simplify management, though this approach has limited data compared to the replacement strategy. 1
- Recent evidence supports direct initiation without a pretreatment period with ACE inhibitors or ARBs as safe and effective 4
- This strategy is particularly useful in hospitalized patients before discharge 1
Pediatric Indication
Sacubitril/valsartan is indicated for symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged 1 year and older. 2
- The medication reduces NT-proBNP and is expected to improve cardiovascular outcomes in this population 2
Key Contraindications and Precautions
Absolute Contraindications:
- Concomitant use with ACE inhibitors (requires 36-hour washout period when switching from ACE inhibitor) 1, 2
- History of angioedema related to previous ACE inhibitor or ARB therapy 1
- Pregnancy (causes fetal toxicity and death) 2
Relative Contraindications Requiring Dose Adjustment:
- Severe renal impairment (eGFR <30 mL/min/1.73 m²): start with 24/26 mg twice daily 4
- Moderate hepatic impairment (Child-Pugh B): start with 24/26 mg twice daily 4, 2
- Age ≥75 years: start with 24/26 mg twice daily 4
Important Safety Considerations:
- Asymptomatic hypotension is NOT a contraindication and should not prevent initiation or uptitration, as benefits are maintained even with systolic BP <110 mmHg 4
- Monitor blood pressure, renal function, and serum potassium regularly, especially when combined with mineralocorticoid receptor antagonists 4
- Exercise caution when serum potassium >5.0 mEq/L 4
Common Pitfalls to Avoid
- Do not wait for patients to "fail" optimal medical therapy before switching from ACE inhibitor/ARB to sacubitril/valsartan—all symptomatic HFrEF patients on ACE inhibitors or ARBs are candidates 4
- Do not avoid initiation due to asymptomatic hypotension or borderline blood pressure (systolic BP ≥100 mmHg preferred but lower BP not absolute contraindication) 4
- Do not fail to titrate to target dose of 97/103 mg twice daily—medium-range doses do not provide most of the benefits 4
- Do not permanently reduce dose when temporary reduction with subsequent re-titration would be more appropriate 4