In a patient with end-stage renal disease on sacubitril/valsartan (Entresto) who has an estimated glomerular filtration rate of 6 mL/min/1.73 m² and no edema, should the medication be stopped, and is it appropriate to start an ACE inhibitor or an ARB?

Continue Entresto with Close Monitoring in ESRD with eGFR 6

In a patient with ESRD on Entresto (sacubitril/valsartan) with an eGFR of 6 mL/min/1.73 m² and no edema, you should generally continue the medication rather than discontinue it, and switching to an ACE inhibitor or ARB is not recommended as these offer inferior outcomes compared to Entresto in heart failure.

Rationale for Continuing Entresto

The most recent KDIGO 2024 guidelines provide critical guidance here. Practice Point 3.6.5 states to "consider reducing the dose or discontinuing ACEi or ARB in the setting of either symptomatic hypotension or uncontrolled hyperkalemia despite medical treatment, or to reduce uremic symptoms while treating kidney failure (eGFR <15 ml/min per 1.73 m²)" 1, 2. Note this says "consider" - not mandate - and specifically applies when there are symptoms or complications, which your patient lacks.

More importantly, Practice Point 3.6.7 explicitly states: "Continue ACEi or ARB in people with CKD even when the eGFR falls below 30 ml/min per 1.73 m²" 1, 2. While this refers to ACE/ARB, the principle extends to Entresto, which contains valsartan (an ARB) plus sacubitril.

The FDA label for Entresto confirms it can be used in severe renal impairment (eGFR <30), though it recommends starting at half the usual dose 3. Since your patient is already established on therapy and tolerating it well (no edema, presumably stable), continuation is appropriate.

Why Not Switch to ACE/ARB?

Switching from Entresto to an ACE inhibitor or ARB would be a therapeutic downgrade. Recent evidence shows:

• Entresto provides superior cardiovascular and mortality benefits compared to ACE/ARB in heart failure 4
• In ESRD patients specifically, systematic reviews demonstrate that sacubitril/valsartan improves left ventricular ejection fraction without increasing risks of hyperkalemia or hypotension compared to standard care 5, 6, 7
• A 2020 study found that discontinuing RAS blockade (ACE/ARB) in patients with eGFR <30 was associated with higher mortality (HR 1.39) and major adverse cardiovascular events (HR 1.37) 8

Monitoring Requirements

Since your patient has severe renal impairment, implement this monitoring protocol:

Within 2-4 weeks of any dose change or clinical concern:

• Serum creatinine and potassium 1, 2, 9
• Blood pressure (assess for symptomatic hypotension)

Ongoing surveillance:

• Monitor for hyperkalemia (K+ >5.5 mmol/L warrants dose reduction; K+ >6.0 mmol/L requires immediate discontinuation) 10
• Watch for symptomatic hypotension (dizziness, lightheadedness, fatigue)
• Assess for uremic symptoms that might warrant dose reduction 2, 9

When to Consider Dose Reduction or Discontinuation

Reduce dose or discontinue Entresto only if:

• Symptomatic hypotension develops despite patient education and management
• Uncontrolled hyperkalemia (K+ >6.0 mmol/L) persists despite potassium-lowering measures 10, 2
• Uremic symptoms worsen and are attributed to the medication 2, 9
• Patient initiates dialysis and develops intradialytic hypotension 11

Do NOT discontinue for:

• Asymptomatic low blood pressure 12, 13
• Creatinine increases ≤30% from baseline 14, 9, 15, 14
• Mild hyperkalemia (K+ 5.0-5.5 mmol/L) - manage with dietary modification, diuretics, or potassium binders first 10, 2

Special Considerations for ESRD

Real-world data shows that dose reduction or discontinuation of sacubitril/valsartan is common in hemodialysis patients (41% in one study), often due to hypotension concerns 11. However, patients who continued therapy without dose reduction had better outcomes, suggesting clinicians may be overly cautious.

The 2025 consensus statement on heart failure with low blood pressure emphasizes that asymptomatic low blood pressure should not prompt medication changes 13. Focus instead on optimizing volume status and addressing other causes of hypotension.

Bottom Line Algorithm

1. Continue current Entresto dose if patient is asymptomatic
2. Check potassium and creatinine within 2-4 weeks
3. If K+ 5.5-6.0 mmol/L: Reduce dietary potassium, optimize diuretics, consider potassium binders - do NOT stop Entresto initially
4. If K+ >6.0 mmol/L or symptomatic hypotension: Reduce Entresto dose by 50% or discontinue temporarily, seek nephrology input
5. Never switch to ACE/ARB - this provides inferior heart failure outcomes
6. If dialysis is initiated: Continue Entresto but monitor closely for intradialytic hypotension

The absence of edema in your patient suggests good volume management, which reduces concerns about medication-related hypotension. This patient represents an ideal candidate for continuing Entresto through advanced CKD.