Is sacubitril/valsartan (Angiotensin Receptor-Neprilysin Inhibitor) used in the treatment of acute myocardial infarction?

Sacubitril/Valsartan in Acute Myocardial Infarction

Sacubitril/valsartan is not recommended as first-line therapy in acute myocardial infarction, but may be considered as an alternative to ACE inhibitors or ARBs in specific patients with left ventricular systolic dysfunction after MI. 1

Current Guideline Recommendations

First-Line Therapy

• ACE inhibitors remain the first-line therapy in acute MI, particularly for patients with:

  • Anterior MI location
  • Heart failure
  • Ejection fraction ≤40%
  • Diabetes mellitus 1

• ACE inhibitors should be started within the first 24 hours of STEMI in these high-risk patients 1

Role of ARBs and Sacubitril/Valsartan

• ARBs (preferably valsartan) are recommended as alternatives for patients who are intolerant to ACE inhibitors 1

• According to the 2017 ACC/AHA guidelines, sacubitril/valsartan can fulfill the criteria for ARB therapy in post-MI patients with left ventricular systolic dysfunction (LVSD) 1

• However, the PARADISE-MI trial (2021) showed that sacubitril/valsartan was not significantly better than ramipril in reducing cardiovascular death or incident heart failure in acute MI patients (HR 0.90,95% CI 0.78-1.04, p=0.17) 2

Evidence-Based Algorithm for Use

1. Initial Assessment:

   • Evaluate for LVSD (LVEF <40%)
   • Check for signs of heart failure
   • Assess anterior MI location

2. First-Line Therapy:

   • Start ACE inhibitor within 24 hours of MI onset in eligible patients
   • Monitor for hypotension, renal dysfunction, and hyperkalemia

3. When to Consider Sacubitril/Valsartan:

   • For patients intolerant to ACE inhibitors (e.g., angioedema, cough)
   • For patients with established heart failure with reduced ejection fraction after MI
   • Not as initial therapy during the acute phase of MI

Safety Considerations

• Hypotension Risk: Sacubitril/valsartan has a higher incidence of hypotension (28.3%) compared to ACE inhibitors (21.9%) in post-MI patients 3

• Drug Interactions: Sacubitril/valsartan may interact with statins that are substrates of OATP1B1, OATP1B3, OAT1, and OAT3 transporters 1

• Contraindications: Should not be used concurrently with ACE inhibitors due to increased risk of angioedema 1

• Timing: Wait at least 36 hours after discontinuing ACE inhibitor before initiating sacubitril/valsartan to reduce angioedema risk

Potential Benefits in Selected Patients

Some smaller studies suggest potential benefits of sacubitril/valsartan in specific post-MI populations:

• May improve left ventricular ejection fraction and decrease NT-proBNP levels at 3-6 months post-MI 4

• May reduce left ventricular remodeling parameters (LVEDD, LVEDVI, LVESVI) 4

• In diabetic patients with heart failure with midrange ejection fraction after AMI, sacubitril/valsartan showed better improvement in left ventricular function compared to valsartan alone 5

Conclusion

While sacubitril/valsartan is an established therapy for chronic heart failure with reduced ejection fraction, current evidence does not support its routine use as first-line therapy in acute myocardial infarction. ACE inhibitors remain the standard of care in the acute setting, with ARBs as alternatives for intolerant patients. Sacubitril/valsartan may be considered in selected patients with established left ventricular dysfunction after the acute phase of MI, particularly those who are intolerant to ACE inhibitors.