Should Entresto (sacubitril/valsartan) be discontinued in a patient with a history of heart failure that has been resolved?

Should Entresto Be Discontinued in Resolved Heart Failure?

No, Entresto should not be discontinued in patients with a history of heart failure that has "resolved" or improved, as heart failure with reduced ejection fraction is a chronic progressive condition requiring lifelong disease-modifying therapy to prevent recurrence, hospitalization, and death. 1

Understanding "Resolved" Heart Failure

The concept of "resolved" heart failure is misleading in clinical practice. Heart failure with reduced ejection fraction (HFrEF) is a chronic, progressive syndrome requiring continuous neurohormonal blockade even when symptoms improve or ejection fraction normalizes. 1, 2

• Symptom improvement does not equal disease resolution: Patients may feel better and have improved functional status due to effective medical therapy, but the underlying cardiac remodeling and neurohormonal activation persist. 3
• Discontinuation leads to decompensation: Stopping guideline-directed medical therapy, including Entresto, typically results in clinical deterioration, rehospitalization, and increased mortality risk. 1

Why Entresto Should Be Continued

Entresto provides sustained mortality and morbidity benefits that are lost upon discontinuation. The drug reduces cardiovascular death by 20% and heart failure hospitalization by 21% compared to ACE inhibitors in patients with HFrEF. 1

Disease-Modifying Effects

• Entresto reduces all-cause mortality by 16% in HFrEF patients, a benefit that requires ongoing therapy to maintain. 1
• The medication works through dual mechanisms—neprilysin inhibition and angiotensin receptor blockade—that actively prevent cardiac remodeling and disease progression. 3, 2
• Clinical guidelines recommend Entresto as replacement therapy for ACE inhibitors in symptomatic HFrEF patients (NYHA class II-III) who remain on chronic therapy indefinitely. 4

Evidence for Long-Term Continuation

• The PARADIGM-HF trial, which established Entresto's superiority over enalapril, was designed as a chronic treatment study with no planned discontinuation in responders. 2
• Guidelines from the European Society of Cardiology and American College of Cardiology/American Heart Association recommend Entresto for patients with current or prior LVEF ≤40%, emphasizing continuation even after improvement. 4, 1

Clinical Approach to "Improved" Patients

Continue Entresto at the maximally tolerated dose, aiming for target dosing of 97/103 mg twice daily. 5

Monitoring Strategy

• Reassess LVEF, NT-proBNP levels, and functional status every 3-6 months to confirm sustained improvement on therapy. 6, 5
• Monitor blood pressure, renal function (eGFR), and potassium levels regularly, as these determine tolerability rather than need for discontinuation. 7
• If patients develop hypotension or other dose-limiting side effects, reduce the dose rather than discontinue entirely. 3, 2

Common Pitfall to Avoid

The most critical error is discontinuing Entresto because the patient "feels better" or has normalized ejection fraction. This improvement is a therapeutic success that requires ongoing treatment to maintain, not a reason to stop. 1, 2

• Patients who discontinue disease-modifying therapy after clinical improvement have significantly higher rates of heart failure rehospitalization and cardiovascular events. 6
• Even patients with recovered LVEF remain at elevated risk for recurrent heart failure if neurohormonal blockade is withdrawn. 1

Exceptions Requiring Discontinuation

Entresto should only be discontinued for specific contraindications or intolerable adverse effects:

• History of angioedema related to previous ACE inhibitor, ARB, or Entresto therapy. 1
• Severe hypotension unresponsive to dose reduction that compromises organ perfusion. 3, 2
• Severe renal failure or hyperkalemia that cannot be managed with dose adjustment or supportive measures. 7
• Patient refusal or cost barriers after thorough counseling about risks of discontinuation. 4

In these situations, substitute with alternative guideline-directed medical therapy (ACE inhibitor or ARB plus beta-blocker plus MRA) rather than leaving the patient without neurohormonal blockade. 4, 1