Entresto Should Not Be Routinely Started Before Valve Replacement Surgery
Entresto (sacubitril/valsartan) is not indicated for patients preparing for aortic or mitral valve replacement surgery unless they have established heart failure with reduced ejection fraction (HFrEF) that meets standard criteria for ARNI therapy. The decision to initiate Entresto should be based on the presence of HFrEF (LVEF ≤40%), not simply because valve surgery is planned.
Clinical Context and Guideline Framework
The 2020 ACC/AHA valvular heart disease guidelines 1, 2 provide comprehensive recommendations for valve replacement timing but make no mention of initiating ARNI therapy as part of preoperative preparation. The guidelines focus on:
- Symptom status (NYHA class)
- Left ventricular systolic function (LVEF <55% triggers intervention consideration)
- LV dimensions (LVESD >50 mm or indexed >25 mm/m²)
- Concurrent cardiac procedures
Notably, medical optimization before valve surgery centers on managing heart failure symptoms with diuretics, addressing atrial fibrillation, and anticoagulation management 3, 4—not on initiating novel neurohormonal blockade.
When Entresto IS Appropriate in the Valve Surgery Context
Established HFrEF Criteria Must Be Met
Entresto is FDA-approved and guideline-recommended for patients with chronic HFrEF 5. If your patient has:
- LVEF ≤40% (some guidelines extend to <50%)
- NYHA class II-IV symptoms
- Tolerance of ACE inhibitor or ARB (or is ACE-I/ARB naïve)
Then Entresto should be initiated regardless of planned valve surgery, following standard HFrEF protocols 6, 7.
Post-Operative HFrEF Development
Recent evidence suggests a role for Entresto after valve surgery in patients who develop HFrEF:
- Approximately 8% of patients with preoperative LVEF ≥50% develop HFrEF (LVEF ≤40%) after cardiac valve surgery 8
- Sacubitril/valsartan initiated post-operatively in these patients demonstrates significant improvement in LVEF and left ventricular remodeling compared to standard therapy 8
- In patients with AMI complicated by moderate-to-severe mitral regurgitation, early ARNI administration after revascularization significantly reduced mitral regurgitation severity and improved ventricular remodeling 9
Specific Algorithmic Approach
Preoperative Assessment:
Measure baseline LVEF accurately (echocardiography preferred)
If LVEF >40-50%:
If LVEF ≤40% with HF symptoms:
- Initiate Entresto per standard HFrEF protocols 6, 7
- Start at 49/51 mg twice daily (or 24/26 mg if ACE-I/ARB naïve or severe renal impairment) 5
- Allow 36-hour washout if switching from ACE inhibitor 5
- Uptitrate to target dose 97/103 mg twice daily as tolerated
- Do not delay necessary valve surgery for medication optimization
Postoperative Management:
Obtain echocardiography 2-4 weeks post-surgery to assess LVEF 3
If post-operative LVEF ≤40% develops:
If significant mitral regurgitation persists or develops post-operatively:
- Consider Entresto initiation, as recent data show mortality benefit in HFrEF with significant MR 11
Critical Safety Considerations
Hypotension Risk
- Sacubitril/valsartan causes more hypotension than ACE inhibitors 6, 9
- Patients with systolic BP <100 mmHg should not receive Entresto 5
- In the perioperative period, volume status fluctuates significantly—ensure adequate preload before initiation
- Consider empiric reduction of loop diuretics when starting Entresto to mitigate hypotension 7
Hyperkalemia Monitoring
- When combining Entresto with mineralocorticoid receptor antagonists (common in HFrEF), hyperkalemia risk increases significantly (10% incidence vs 0% without MRA) 10
- Monitor potassium within 1-2 weeks of initiation, especially if concurrent spironolactone use
Newly Recognized Coagulopathy
- Recent case reports identify isolated PT/INR elevation with Entresto in the absence of anticoagulation 12, 13
- Consider baseline and periodic coagulation monitoring, particularly in patients at elevated bleeding risk
- This is especially relevant in the perioperative period when bleeding complications are most consequential
Contraindications
- History of angioedema (absolute contraindication) 5
- Concomitant ACE inhibitor use (requires 36-hour washout) 5
- Pregnancy (discontinue immediately if detected) 5
Common Pitfalls to Avoid
Do not initiate Entresto simply because valve surgery is planned—there is no evidence supporting this approach and it may introduce unnecessary perioperative risk
Do not delay indicated valve surgery to optimize medical therapy—the 2020 ACC/AHA guidelines emphasize that symptomatic severe valve disease or LV dysfunction warrants prompt surgical intervention 1, 2
Do not assume preserved LVEF preoperatively means no HFrEF risk—8% will develop post-operative HFrEF and may benefit from Entresto 8
Do not overlook volume status when initiating Entresto perioperatively—the combination of neprilysin inhibition and ARB activity creates substantial vasodilation that requires adequate preload
Do not forget the 36-hour ACE-I washout—concurrent use is contraindicated due to angioedema risk 5
Evidence Quality Assessment
The recommendations against routine preoperative Entresto initiation are based on:
- Absence of evidence in major valve disease guidelines 1, 2, 4, 14
- FDA labeling that specifies HFrEF indications without mention of preoperative valve surgery 5
- Established HFrEF trial data (PARADIGM-HF) that excluded patients based on hemodynamic instability, not valve disease per se 5, 15, 16
The recommendations supporting post-operative use in selected patients are based on:
- Recent observational data showing benefit in valve surgery-induced HFrEF 8
- Randomized trial data in AMI with mitral regurgitation 9
- Retrospective cohort data showing mortality benefit in HFrEF with significant MR 11
The evidence strongly supports a "treat the HFrEF, not the valve disease" approach.