How should sacubitril/valsartan (Entresto) be managed perioperatively in a patient undergoing anesthesia, including timing of discontinuation, laboratory monitoring, and resumption after surgery?

Perioperative Management of Entresto (Sacubitril/Valsartan)

Continue Entresto throughout the perioperative period in patients with compensated heart failure undergoing noncardiac surgery, as guideline-directed medical therapy (GDMT) should be maintained to reduce the risk of worsening heart failure, unless specific contraindications arise. 1

Key Management Principles

The 2024 AHA/ACC perioperative guideline explicitly recommends continuing GDMT (excluding SGLT2 inhibitors) in patients with compensated heart failure undergoing noncardiac surgery 1. While the guideline does not specifically address sacubitril/valsartan separately from other renin-angiotensin-aldosterone system (RAAS) inhibitors, the evidence supports continuation based on the following framework:

Preoperative Considerations

Do NOT routinely discontinue Entresto before surgery. The guideline emphasizes that delaying resumption of ACE inhibitors/ARBs postoperatively increases 30-day mortality risk 1. Recent cardiac surgery data demonstrates that early initiation of sacubitril/valsartan after CABG is safe and effective, with low discontinuation rates (2.5-5.2%) and rare adverse events 2. A 2026 study in cardiac surgery patients found no difference in vasoactive-inotropic scores or postoperative hemodynamic instability between patients on sacubitril/valsartan versus controls 3.

Critical caveat: Older research on angiotensin II antagonists (from 2001) showed increased hypotensive episodes during anesthetic induction when continued 4. However, this conflicts with current guideline recommendations and more recent evidence showing safety of continuation 1, 2, 3.

Intraoperative Monitoring

• Blood pressure targets: Maintain MAP ≥60-65 mm Hg or SBP >90 mm Hg 1
• Hypotension management: Be prepared for potential increased hypotension risk during induction, though recent data suggests this may be overstated 3
• Fluid and vasopressor readiness: Have ephedrine, phenylephrine, or norepinephrine immediately available

The FDA label warns that Entresto lowers blood pressure and may cause symptomatic hypotension, particularly in volume-depleted patients 5. Correct volume depletion before surgery if present.

Laboratory Monitoring

Monitor these parameters perioperatively:

• Serum creatinine: Watch for >50% increases, which occur in ~16-17% of patients 5. The drug can cause acute renal failure in RAAS-dependent patients 5
• Serum potassium: Check for hyperkalemia (>5.5 mEq/L occurs in ~16-18% of patients) 5. Risk factors include severe renal impairment, diabetes, and high potassium diet 5
• Hemoglobin/hematocrit: Monitor for >20% decreases (occurs in ~5-7% of patients) 5
• Coagulation parameters: Emerging evidence suggests potential bleeding risk with elevated PT/INR, even without anticoagulants 6. This is a newly recognized adverse effect requiring vigilant monitoring in high-risk patients.

Postoperative Management

Resume Entresto as soon as clinically reasonable once the patient is hemodynamically stable and able to take oral medications 1. The guideline explicitly states that delaying resumption of RAAS inhibitors increases mortality risk.

Restart criteria:

• Hemodynamically stable (MAP ≥60-65 mm Hg without escalating vasopressor support)
• Adequate oral intake
• No acute kidney injury requiring intervention
• Potassium <5.5 mEq/L

Studies in cardiac surgery patients show successful early postoperative initiation (within days) with significant NT-proBNP reduction and improved outcomes 2, 7.

Special Situations

If hypotension occurs perioperatively:

• Administer IV fluids first
• Use vasopressors as needed (ephedrine, phenylephrine, norepinephrine)
• Consider temporary dose reduction rather than complete discontinuation 5
• Permanent discontinuation is usually not required 5

Angioedema risk: Entresto carries a 0.5% angioedema risk (2.4% in Black patients) 5. Have airway management equipment and epinephrine 1:1000 (0.3-0.5 mL subcutaneous) immediately available 5.

Renal dysfunction: If creatinine rises significantly, down-titrate or temporarily interrupt rather than permanently discontinue 5.

Bottom Line Algorithm

1. Continue Entresto through surgery in compensated heart failure patients
2. Ensure euvolemia before anesthetic induction
3. Monitor BP closely during induction; treat hypotension aggressively with fluids/vasopressors
4. Check labs postoperatively: creatinine, potassium, hemoglobin, consider PT/INR in high-risk patients
5. Resume immediately when hemodynamically stable and taking oral medications

This approach prioritizes mortality reduction over theoretical hypotension risk, aligning with the highest-quality 2024 guideline evidence 1.