What is the role of Angiotensin-Converting Enzyme (ACE) inhibitors in the management of acute Myocardial Infarction (MI)?

Role of ACE Inhibitors in Acute Myocardial Infarction

ACE inhibitors should be started within the first 24 hours of STEMI in patients with evidence of heart failure, left ventricular systolic dysfunction, diabetes, or an anterior infarct to reduce mortality and prevent adverse cardiac remodeling. 1

Indications for ACE Inhibitors in Acute MI

• ACE inhibitors are recommended to be started within the first 24 hours of STEMI in specific high-risk patients including those with:

  • Evidence of heart failure
  • Left ventricular systolic dysfunction (LVEF < 40%)
  • Diabetes mellitus
  • Anterior wall infarction 1

• ACE inhibitors should be administered as soon as the patient is hemodynamically stable for all patients with evidence of LVEF < 40% and/or heart failure to reduce the risk of hospitalization and death 1

• Several major trials (SAVE, AIRE, TRACE) have established that ACE inhibitors reduce mortality after acute myocardial infarction with reduced residual left ventricular function 1

Clinical Benefits of ACE Inhibitors in Acute MI

• In the TRACE study, trandolapril reduced mortality from 42.3% to 34.7% (a 27% relative reduction) when started a median of 4 days after infarction in patients with left ventricular dysfunction 1, 2

• The AIRE trial demonstrated mortality reduction from 22.6% to 16.9% (a 27% relative reduction) when ramipril was started a mean of 5 days after MI onset in patients with clinical or radiological features of heart failure 1

• ACE inhibitors provide significant reduction in:

  • Overall mortality
  • Cardiovascular mortality
  • Development of severe heart failure
  • Risk of hospitalization 1, 3

• The GISSI-3 trial showed that patients receiving lisinopril had an 11% lower risk of death compared to patients who did not receive lisinopril at six weeks post-MI 4

Timing and Duration of Therapy

• ACE inhibitors should be started within the first 24 hours of STEMI in indicated patients 1

• The benefits of ACE inhibitor therapy are observed early, with most mortality benefit seen within the first week of treatment 3

• Follow-up data from post-infarction studies and the HOPE trial suggest a benefit if administration of an ACE inhibitor is continued for at least 4 to 5 years, even in the absence of ventricular dysfunction 1

• ACE inhibitor therapy should be continued long-term (indefinitely) in patients who tolerate this class of medication 1, 5

Cautions and Contraindications

• Against early ACE inhibitor use is the increased incidence of hypotension and renal failure in those receiving ACE inhibitors in the acute stage 1

• Patients with acute myocardial infarction treated with lisinopril had a higher incidence of:

  • Persistent hypotension (9.0% versus 3.7%)
  • Renal dysfunction (2.4% versus 1.1%) 4

• ACE inhibitors should be used with caution in patients with:

  • Hypotension (systolic blood pressure < 90 mmHg)
  • Severe renal dysfunction
  • Hyperkalemia 1

Alternative Therapies

• An ARB, preferably valsartan, is an alternative to ACE inhibitors in patients with heart failure and/or LV systolic dysfunction, particularly those who are intolerant of ACE inhibitors 1

• The VALIANT trial demonstrated that valsartan was as effective as captopril in patients following an acute MI with heart failure and/or LV systolic dysfunction 6, 7

• There was no additional benefit when combining valsartan and captopril compared to captopril alone in post-MI patients 6

Dosing Considerations

• Despite guideline recommendations, studies show that many MI patients with left ventricular dysfunction do not receive ACE inhibitors, and when used, the doses prescribed are often markedly smaller than target doses used in clinical trials 8

• The ATLAS study showed that high-dose lisinopril reduced the combined outcome of all-cause mortality and HF hospitalization by 15% compared to low-dose lisinopril, with a 24% reduction in HF hospitalization 7

• Patients should be titrated to the target doses used in clinical trials that established efficacy 8, 7

Practical Algorithm for ACE Inhibitor Use in Acute MI

1. Assess for indications:

   • LVEF < 40%
   • Clinical heart failure
   • Anterior MI
   • Diabetes mellitus 1

2. Check for contraindications:

   • Hypotension (systolic BP < 90 mmHg)
   • Severe renal dysfunction
   • History of angioedema with ACE inhibitors
   • Pregnancy 1, 4

3. If indicated and no contraindications:

   • Start ACE inhibitor within first 24 hours of MI
   • Begin with low dose and titrate as tolerated
   • Monitor blood pressure and renal function 1, 4

4. If ACE inhibitor not tolerated:

   • Consider ARB (preferably valsartan) as alternative 1, 6

5. Continue therapy long-term (indefinitely) if tolerated 1, 5