Must I start an Angiotensin-Converting Enzyme (ACE) inhibitor in all patients with Non-ST-Elevation Myocardial Infarction (NSTEMI)?

ACE Inhibitors in NSTEMI Patients

ACE inhibitors should not be started in all patients with NSTEMI, but rather should be given and continued indefinitely in specific patient populations: those with LVEF less than 0.40, hypertension, diabetes mellitus, or stable chronic kidney disease, unless contraindicated. 1

Indications for ACE Inhibitors in NSTEMI

ACE inhibitors have a Class I recommendation (Level of Evidence: A) for the following NSTEMI patients:

• Left ventricular ejection fraction (LVEF) less than 0.40
• Hypertension
• Diabetes mellitus
• Stable chronic kidney disease (CKD)

In these high-risk populations, ACE inhibitors should be started and continued indefinitely unless contraindicated 1.

Reasonable Use in Lower-Risk Patients

For NSTEMI patients who don't meet the above criteria:

• ACE inhibitors may be reasonable in all other patients with cardiac or other vascular disease (Class IIb, Level of Evidence: B) 1
• The decision should be based on the patient's overall cardiovascular risk profile

Timing of ACE Inhibitor Initiation

• For patients with pulmonary congestion or LVEF ≤0.40, an ACE inhibitor should be administered orally within the first 24 hours 1
• This early administration is contraindicated in patients with:
  • Hypotension (systolic blood pressure <100 mmHg or <30 mmHg below baseline)
  • Other known contraindications to ACE inhibitors

Alternatives for ACE Inhibitor-Intolerant Patients

For patients who cannot tolerate ACE inhibitors:

• Angiotensin receptor blockers (ARBs) are recommended (Class I, Level of Evidence: A) for patients with:
  • Heart failure or MI with LVEF ≤0.40 1
  • Hypertension (Class I, Level of Evidence: B) 1

Clinical Evidence Supporting These Recommendations

The recommendations are supported by multiple large clinical trials:

• The HOPE and EUROPA studies showed benefits of ACE inhibitors in patients with coronary artery disease, with greater absolute benefit proportional to disease-related risk 1
• The GISSI-3 trial demonstrated that lisinopril reduced mortality in patients with acute MI, with greater benefit in STEMI (11/1000 patients saved) compared to NSTEMI (only 1/1000 patients saved) 2, 3
• More recent research suggests that in NSTEMI patients who undergo successful PCI, ACE inhibitors/ARBs are associated with lower 4-year all-cause mortality 4

Common Pitfalls and Caveats

1. Avoid indiscriminate use: Not all NSTEMI patients require ACE inhibitors; target those with specific indications
2. Monitor for adverse effects:
   • Hypotension
   • Worsening renal function (especially in patients with pre-existing renal disease)
   • Hyperkalemia
   • Cough
3. Dose considerations: Target doses should match those achieved in clinical trials
4. Contraindications: Bilateral renal artery stenosis, pregnancy, history of angioedema, hyperkalemia

Algorithmic Approach to ACE Inhibitor Use in NSTEMI

1. Assess LVEF (via echocardiography, nuclear ventriculography, MRI, or CT angiography)
2. Determine presence of hypertension, diabetes, or CKD
3. Check for contraindications:
   • Hypotension (SBP <100 mmHg)
   • History of angioedema
   • Bilateral renal artery stenosis
   • Pregnancy
   • Hyperkalemia
4. If LVEF ≤0.40 OR hypertension OR diabetes OR CKD present AND no contraindications:
   • Start ACE inhibitor within 24 hours if possible
   • Continue indefinitely
5. If none of these conditions present:
   • Consider ACE inhibitor based on overall cardiovascular risk
   • May be reasonable but not mandatory
6. If ACE inhibitor not tolerated:
   • Switch to ARB, especially if LVEF ≤0.40 or hypertension present

In conclusion, while ACE inhibitors provide significant mortality and morbidity benefits in specific NSTEMI populations, they are not indicated for universal use in all NSTEMI patients.