How long can a patient with heart failure with reduced ejection fraction safely be without Entresto (sacubitril/valsartan)?

How Long Can a Patient Be Without Entresto (Sacubitril/Valsartan)?

Patients with heart failure with reduced ejection fraction (HFrEF) should not discontinue Entresto (sacubitril/valsartan) for any extended period as it is a cornerstone therapy that reduces mortality and hospitalization risk. If interruption is absolutely necessary, it should be limited to the shortest possible time, ideally not exceeding 1-2 weeks.

Understanding Entresto's Role in HFrEF Management

Entresto (sacubitril/valsartan) is an angiotensin receptor-neprilysin inhibitor (ARNI) that plays a critical role in the treatment algorithm for HFrEF. According to the 2016 ESC guidelines, it is recommended for patients with HFrEF who remain symptomatic despite optimal medical therapy 1.

The importance of Entresto is highlighted by its:

• Significant mortality benefit (reduction in cardiovascular death)
• Reduction in heart failure hospitalizations
• Improvement in cardiac remodeling
• Enhancement of quality of life

Risks of Discontinuation

Discontinuing Entresto may lead to:

• Increased risk of cardiovascular mortality
• Higher likelihood of heart failure hospitalization
• Worsening of heart failure symptoms
• Reversal of beneficial cardiac remodeling effects

Guidance for Unavoidable Interruptions

If Entresto must be temporarily discontinued:

1. Duration: Keep the interruption as brief as possible (ideally less than 1-2 weeks)
2. Alternative Coverage: Consider temporarily substituting with an ACE inhibitor or ARB (but not both)
   • Note: Allow a 36-hour washout period when switching from Entresto to an ACE inhibitor to reduce angioedema risk
3. Monitoring: Increase monitoring of symptoms, vital signs, and volume status during the interruption
4. Restart: Resume Entresto as soon as possible, starting at a lower dose if the interruption was prolonged

Special Considerations

For Different Patient Populations:

• Patients with advanced heart failure (NYHA Class IV): These patients may be particularly vulnerable to interruptions, though evidence specifically for this population is limited 2
• Newly diagnosed HFrEF: Patients with shorter duration of heart failure (<12 months) showed particularly impressive improvements in ejection fraction (12.2%) with Entresto in studies 3, suggesting interruptions may be especially detrimental

For Different Durations of Interruption:

• Short-term (days): Minimal risk if other HF medications continued
• Medium-term (1-2 weeks): Increasing risk of decompensation
• Long-term (>2 weeks): Significant risk of disease progression and loss of beneficial cardiac remodeling

Practical Algorithm for Managing Entresto Interruption

1. Assess necessity of interruption:

   • Is it absolutely required (e.g., surgery, severe adverse reaction)?
   • Can the interruption be avoided or minimized?

2. If interruption necessary:

   • Ensure patient continues other guideline-directed medical therapy
   • Consider temporary substitution with ACE inhibitor or ARB
   • Intensify monitoring of symptoms and vital signs
   • Educate patient on warning signs requiring immediate attention

3. Upon restarting:

   • If interruption <1 week: Resume previous dose
   • If interruption >1 week: Consider restarting at lower dose and titrating up
   • Monitor blood pressure, renal function, and potassium levels closely

Conclusion

While specific data on the exact "safe" duration for Entresto interruption is limited, the significant mortality and morbidity benefits of this medication suggest that any interruption should be kept as brief as possible. The risks of discontinuation likely outweigh the benefits in most scenarios, and alternative strategies should be considered whenever possible.