Should sacubitril‑valsartan (Entresto) be discontinued in a patient with non‑ischemic cardiomyopathy after left‑ventricular ejection fraction has recovered?

Should Entresto Be Stopped After EF Recovery in Non-Ischemic Cardiomyopathy?

No, Entresto (sacubitril-valsartan) should not be stopped in patients with non-ischemic cardiomyopathy even after ejection fraction has recovered. The evidence strongly demonstrates that discontinuing or tapering this medication leads to deterioration of cardiac function and worse clinical outcomes.

The Evidence Against Discontinuation

The most compelling data comes from real-world studies examining what happens when patients stop sacubitril-valsartan after achieving EF recovery. In a 2020 study of 437 heart failure patients, 77 achieved LVEF recovery to ≥50% 1. Among these recovered patients, those who continued the same dose of sacubitril-valsartan maintained significantly higher LVEF (56.4 ± 5.3% vs. 45.0 ± 12.8%, p < 0.001) compared to those who either tapered the dose or switched back to ACE inhibitors/ARBs 1. More critically, cardiovascular death or heart failure hospitalization occurred in 23.1% of patients who tapered versus only 5.9% who maintained therapy (HR 0.22, p = 0.035) 1.

A 2021 study reinforces this finding even more dramatically 2. Patients who discontinued sacubitril-valsartan after ≥5 months and switched back to ACE inhibitors or ARBs showed worsening of both NYHA functional class and LVEF (p = 0.001 for both parameters) despite being compliant with optimal conventional therapy 2. This deterioration occurred even though these patients were receiving evidence-based doses of ACE inhibitors or ARBs—the very medications they were taking before sacubitril-valsartan.

Guideline Framework for Continuation

Current Canadian and American guidelines do not support discontinuation of guideline-directed medical therapy (GDMT) after EF recovery 3, 4. The 2021 CCS/CHFS guidelines explicitly state that GDMT for HFrEF should be continued at the usual dose unless specific intolerances develop 3. The framework emphasizes that if there are concerns about medication use, the dose should be decreased by half and the patient reassessed—but the previous tolerated dose should be resumed as soon as safely possible 3, 4.

The 2020 European framework for describing adherence to heart failure therapy makes no provision for discontinuation based on EF recovery 5. Status I (optimal adherence) is defined as receiving target doses of sacubitril-valsartan (97/103 mg twice daily), regardless of current ejection fraction 5.

Why Recovery Doesn't Mean Cure

The pathophysiology of non-ischemic cardiomyopathy involves ongoing neurohormonal activation and adverse remodeling that sacubitril-valsartan actively suppresses. EF recovery represents successful disease control, not disease resolution. When the medication is withdrawn, the underlying disease process reasserts itself:

• Reverse remodeling reverses: Studies show that LVEF improvement with sacubitril-valsartan depends on continued therapy 1, 6, 7
• Neurohormonal reactivation: Even switching to ACE inhibitors/ARBs (which also block the renin-angiotensin system) cannot prevent deterioration after sacubitril-valsartan discontinuation 2
• Clinical decompensation: The deterioration is not just echocardiographic—patients experience worsening symptoms and increased hospitalizations 1, 2

Predictors of Recovery (But Not Reasons to Stop)

While certain factors predict better EF recovery with sacubitril-valsartan—non-ischemic etiology, smaller baseline LV end-diastolic diameter, higher initial dosing 1, baseline LVEF >30% 6, 8, and female sex 8—none of these factors justify discontinuation after recovery. These predictors help identify who will benefit most, not who can safely stop therapy.

Practical Management Algorithm

For patients with non-ischemic cardiomyopathy who achieve EF recovery on sacubitril-valsartan:

1. Continue sacubitril-valsartan at the same dose indefinitely 1

2. Monitor LVEF every 1-3 years or with clinical status change 4

3. Only consider dose reduction (not discontinuation) if:

   • Documented symptomatic hypotension persists despite adjusting other medications 3, 4
   • Serum creatinine doubles 3
   • Serum potassium ≥5.5 mmol/L despite management 3
   • Intolerable drug-related symptoms that persist despite medication adjustments 3

4. If dose reduction is necessary, reduce by half and reassess—then uptitrate back to the previous tolerated dose as soon as safely possible 3, 4

Common Pitfalls to Avoid

Do not:

• Assume EF normalization means the patient is "cured" and can stop medications
• Switch back to ACE inhibitors/ARBs thinking they provide equivalent protection after recovery—they don't 2
• Taper sacubitril-valsartan gradually thinking this is safer—the evidence shows harm even with tapering 1
• Discontinue due to cost concerns without discussing the clinical consequences with the patient

The FDA label for Entresto provides no guidance on discontinuation based on EF recovery 9, and the warnings focus on situations requiring temporary interruption (pregnancy, angioedema, life-threatening complications) rather than elective discontinuation after clinical improvement 9.

Bottom Line

Sacubitril-valsartan should be continued indefinitely in patients with non-ischemic cardiomyopathy, even after EF recovery. The medication is maintaining the recovery, not just treating the initial dysfunction. Discontinuation leads to measurable deterioration in cardiac function and worse clinical outcomes, including increased hospitalizations and cardiovascular events 1, 2. This represents a fundamental principle: successful treatment of chronic heart failure requires ongoing therapy to maintain benefits.