Is Entresto (sacubitril/valsartan) contraindicated in patients with aortic valve stenosis?

Entresto (Sacubitril/Valsartan) in Aortic Valve Stenosis

Entresto (sacubitril/valsartan) is not specifically contraindicated in patients with aortic valve stenosis, but should be used with caution, starting at low doses with gradual titration under close monitoring.

Rationale for Use in Aortic Stenosis

Renin-angiotensin system (RAS) blockade, which is a component of Entresto through its valsartan moiety, may actually be beneficial in patients with aortic stenosis due to:

• Potentially beneficial effects on left ventricular fibrosis 1
• Improved control of hypertension in patients with concurrent AS and hypertension 1
• Reduction of dyspnea and improved effort tolerance 1

Guidelines for Antihypertensive Therapy in Aortic Stenosis

The 2017 ACC/AHA guidelines provide specific recommendations for treating hypertension in patients with aortic stenosis:

• Hypertension should be treated with pharmacotherapy in adults with asymptomatic aortic stenosis (Class I, Level B-NR) 1
• Start at a low dose and gradually titrate upward as needed 1
• Careful monitoring is essential due to the "two resistors in series" phenomenon (hypertension plus aortic stenosis) 1

Precautions When Using Entresto in Aortic Stenosis

While not contraindicated, several precautions should be observed:

• Start with low doses: Begin with the lowest possible dose and titrate slowly
• Monitor hemodynamics closely: Watch for hypotension, especially in patients with severe AS
• Cardiologist consultation: For patients with moderate or severe aortic stenosis, consultation or co-management with a cardiologist is preferred for hypertension management 1
• Avoid in hemodynamic instability: Use caution in patients with severe, symptomatic AS who may be hemodynamically unstable

Potential Benefits of Entresto in Aortic Stenosis

Recent research suggests potential benefits of sacubitril/valsartan in pressure-overloaded hearts:

• Superior cardioprotective effects compared to valsartan alone in reducing pressure overload-induced ventricular fibrosis 2
• Protection of ventricular myocytes from mitochondrial dysfunction 2
• Reduction of mitochondrial oxidative stress in response to persistent left ventricular pressure overload 2

Severity-Based Approach

The approach to using Entresto should be guided by AS severity:

• Mild to moderate asymptomatic AS: May use Entresto with careful monitoring
• Severe symptomatic AS: Consider valve intervention (TAVR or SAVR) as the primary treatment 1 rather than focusing solely on medical therapy
• Severe AS with heart failure: Valve intervention should be prioritized, but Entresto may be considered in the interim if the patient has heart failure with reduced ejection fraction

Practical Management Algorithm

1. Assess AS severity and symptoms:

   • If severe symptomatic AS: Prioritize valve intervention 1
   • If mild-moderate AS with hypertension: Consider medical therapy

2. If medical therapy is appropriate:

   • Start Entresto at lowest dose (24/26 mg twice daily)
   • Monitor blood pressure closely after initiation
   • Gradually titrate upward if tolerated

3. Monitor for adverse effects:

   • Hypotension (most common concern)
   • Worsening symptoms of AS
   • Renal dysfunction

4. Regular follow-up:

   • Echocardiography every 6 months for severe AS 3
   • Clinical assessment of symptoms
   • Blood pressure monitoring

Common Pitfalls to Avoid

• Rapid dose escalation: Can cause dangerous hypotension in AS patients
• Ignoring symptoms: New or worsening symptoms may indicate AS progression requiring valve intervention rather than medication adjustment
• Overlooking the need for valve intervention: Medical therapy should not delay appropriate surgical or transcatheter intervention in symptomatic severe AS 4
• Failure to involve a Heart Team: Complex cases should involve multidisciplinary discussion 1

In conclusion, while Entresto is not specifically contraindicated in aortic stenosis, it should be used cautiously with close monitoring. The decision to use Entresto should be balanced against the potential need for valve intervention, particularly in patients with severe symptomatic aortic stenosis.