What monitoring parameters are recommended for a patient with heart failure with reduced ejection fraction (HFrEF) taking Entresto (sacubitril/valsartan)?

Monitoring Parameters for Entresto (Sacubitril/Valsartan) in HFrEF

Patients taking Entresto require regular monitoring of blood pressure, renal function (serum creatinine/eGFR), and serum potassium, with particular vigilance during initiation and dose titration. 1

Essential Monitoring Parameters

Blood Pressure Monitoring

• Monitor blood pressure closely during initiation and with each dose escalation 2, 3
• Symptomatic hypotension should be addressed through patient education and counseling, potentially reducing diuretic doses in non-congested patients rather than discontinuing Entresto 2
• Asymptomatic hypotension (even systolic BP <110 mmHg) should not prevent initiation or uptitration, as efficacy is maintained regardless of baseline blood pressure 2, 4
• If symptomatic hypotension occurs, temporarily reduce the dose rather than permanently discontinuing therapy—40% of patients requiring temporary dose reduction can subsequently be restored to target doses 2

Renal Function Monitoring

• Monitor serum creatinine and eGFR routinely, especially when used with aldosterone antagonists 1, 2
• Worsening renal function may require dose adjustment of Entresto and other medications 1
• Mild creatinine elevation (<0.5 mg/dL increase) is acceptable and does not require dose adjustment 2
• For severe renal impairment (eGFR <30 mL/min/1.73 m²), start at half the usual dose (24/26 mg twice daily) 3

Electrolyte Monitoring

• Serial measurement of serum potassium is critical because hyperkalemia may complicate therapy with angiotensin receptor blockers and aldosterone antagonists 1
• Caution when serum potassium levels >5.0 mmol/L, particularly when Entresto is combined with mineralocorticoid receptor antagonists 1
• Regular checks of serum potassium should be performed according to clinical status 1
• Monitor for hyponatremia, which may be a sign of disease progression and is associated with impaired survival 1

Timing of Monitoring

During Initiation

• Check blood pressure, renal function, and potassium before starting therapy 2, 3
• Monitor closely during the first 2-4 weeks when titrating from starting dose (49/51 mg twice daily) to target dose (97/103 mg twice daily) 2, 4

During Maintenance Therapy

• Continue routine monitoring of serum electrolytes and renal function in all patients with heart failure 1
• Frequency should be adjusted based on clinical status, particularly in patients with impaired renal function or those taking aldosterone antagonists 1

Additional Monitoring Considerations

Natriuretic Peptide Monitoring

• While NT-proBNP levels decrease with Entresto therapy (40-65% reduction over time), using BNP measurements to guide dose titration has not been shown to improve outcomes more effectively than achieving target doses proven in clinical trials 1, 3
• BNP levels (a neprilysin substrate) paradoxically increase with Entresto, while NT-proBNP (not a neprilysin substrate) decreases 3

Angioedema Surveillance

• Monitor for signs and symptoms of angioedema, particularly in patients with prior history of angioedema with ACE inhibitors or ARBs 4, 3
• A 36-hour washout period is mandatory when switching from an ACE inhibitor to avoid angioedema risk 2, 3

Common Monitoring Pitfalls to Avoid

• Do not permanently reduce doses due to asymptomatic hypotension or mild laboratory changes—temporary dose reductions with subsequent re-titration are more appropriate 2
• Do not discontinue therapy for mild renal function changes—mild creatinine elevation is acceptable 2
• Do not fail to titrate to target doses (97/103 mg twice daily) as this provides maximum mortality benefit 2, 4
• Do not use medium-range doses as maintenance therapy—they do not provide most of the benefits of target doses 2