Is Entresto (sacubitril/valsartan) contraindicated in patients with severe mitral regurgitation?

Entresto (Sacubitril/Valsartan) in Severe Mitral Regurgitation

Entresto is not contraindicated in patients with severe mitral regurgitation; in fact, it may be beneficial in cases of secondary mitral regurgitation associated with heart failure with reduced ejection fraction.

Understanding Mitral Regurgitation and Entresto

Mitral regurgitation (MR) can be classified into two main types:

1. Primary (organic) MR: Structural abnormalities of valve components
2. Secondary (functional) MR: Normal valve structure but abnormal function due to LV remodeling/dysfunction

Evidence for Entresto in Mitral Regurgitation

The European Society of Cardiology (ESC) guidelines emphasize that optimal heart failure management should be the first step for all patients with secondary mitral regurgitation 1. This includes guideline-directed medical therapy, which may now incorporate sacubitril/valsartan (Entresto).

Recent research demonstrates that sacubitril/valsartan is actually beneficial in patients with functional MR:

• A randomized controlled trial showed that sacubitril/valsartan reduced mitral regurgitation to a greater extent than valsartan alone in patients with secondary functional MR 2
• The decrease in effective regurgitant orifice area was significantly greater in the sacubitril/valsartan group compared to the valsartan group 2

Management Algorithm for Severe MR with Entresto

For Secondary (Functional) MR:

1. First-line approach: Optimize guideline-directed medical therapy

   • Entresto can be part of this regimen, especially in patients with HFrEF
   • Early administration of sacubitril/valsartan after coronary revascularization in patients with acute myocardial infarction complicated by moderate-to-severe MR significantly reduces mitral regurgitation and improves ventricular remodeling 3

2. Monitor for improvement:

   • Reassess MR severity after optimization of medical therapy 1
   • If MR improves with medical therapy including Entresto, continue medical management

3. Consider intervention if symptoms persist despite optimal medical therapy:

   • Surgery may be considered in patients with severe secondary MR and LVEF >30% who remain symptomatic despite optimal medical management 1
   • Percutaneous edge-to-edge repair may be considered in high-risk surgical patients 1

For Primary (Organic) MR:

1. Primary treatment is surgical repair/replacement
2. Medical therapy including Entresto may be used for symptom management if surgery is not feasible or to optimize condition before surgery
3. No contraindication to using Entresto in these patients

Special Considerations

• Monitor blood pressure: Patients on sacubitril/valsartan may experience hypotension, requiring careful monitoring 3
• Dosing: Start at lower doses and titrate up as tolerated, particularly in patients with hemodynamic compromise from severe MR
• Caution in severe aortic stenosis: While not contraindicated in MR, vasodilators including Entresto should be used carefully in patients with concurrent severe aortic stenosis to avoid hypotension 1

Conclusion

Entresto is not contraindicated in severe mitral regurgitation. In fact, for patients with secondary MR, particularly those with heart failure with reduced ejection fraction, sacubitril/valsartan may provide benefits beyond standard therapy by improving the degree of mitral regurgitation and ventricular remodeling.