What is the role of Angiotensin-Converting Enzyme Inhibitors (ACEi) in secondary prevention after a Non-ST-Elevation Myocardial Infarction (NSTEMI)?

From the Guidelines

Angiotensin-converting enzyme inhibitors (ACEIs) are strongly recommended for secondary prevention after a non-ST-elevation myocardial infarction (NSTEMI) in patients with left ventricular dysfunction, heart failure, hypertension, or diabetes, and should be continued indefinitely unless contraindicated. Patients should start an ACEI within 24 hours of stabilization, with common options including lisinopril (starting at 2.5-5 mg daily, target 20-40 mg daily), ramipril (starting at 2.5 mg daily, target 10 mg daily), or perindopril (starting at 2-4 mg daily, target 8 mg daily) 1.

Key Considerations

• ACEIs provide cardiovascular protection by blocking the renin-angiotensin-aldosterone system, reducing blood pressure, preventing adverse cardiac remodeling, and improving endothelial function.
• They have been shown to reduce mortality, recurrent MI, and heart failure hospitalizations in post-MI patients.
• Contraindications include pregnancy, history of angioedema, bilateral renal artery stenosis, or potassium levels >5.5 mmol/L.
• If a patient cannot tolerate an ACEI due to cough or other side effects, an angiotensin receptor blocker (ARB) can be substituted, particularly in those with clinical or radiological signs of heart failure and left ventricular ejection fraction (LVEF) less than 0.40 1.

Monitoring and Titration

• Start with a low dose and gradually titrate upward over several weeks while monitoring blood pressure and kidney function.
• Regular assessment of renal function and potassium levels is crucial to minimize the risk of adverse effects.
• The use of ACEIs in patients with NSTEMI is supported by high-quality evidence, including guidelines from the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines 1.

Alternative Options

• For patients who are intolerant of ACEIs, ARBs are a reasonable alternative, especially in those with heart failure and LVEF less than 0.40 1.
• The choice of ACEI or ARB should be individualized based on patient-specific factors, including comorbidities, potential side effects, and cost considerations.

From the FDA Drug Label

At the end of the trial, patients in the valsartan group had a blood pressure that was 4 mmHg systolic and 2 mmHg diastolic lower than the placebo group There were two primary end points, both assessed as time to first event: all-cause mortality and heart failure morbidity, the latter defined as all-cause mortality, sudden death with resuscitation, hospitalization for heart failure, and the need for intravenous inotropic or vasodilatory drugs for at least 4 hours. Although the overall morbidity result favored valsartan, this result was largely driven by the 7% of patients not receiving an ACE inhibitor, as shown in the following table. Without ACE Inhibitor With ACE Inhibitor Placebo (N=181) Valsartan (N=185) Placebo (N=2,318) Valsartan (N=2,326) Events (%) 77 (42.5%) 46 (24.9%) 724 (31.2%) 677 (29.1%) Hazard ratio (95% CI) 0. 51 (0.35,0.73) 0.92 (0.82,1.02) p-value 0.0002 0. 0965 The modest favorable trend in the group receiving an ACE inhibitor was largely driven by the patients receiving less than the recommended dose of ACE inhibitor. Thus, there is little evidence of further clinical benefit when valsartan is added to an adequate dose of ACE inhibitor.

The role of Angiotensin-Converting Enzyme Inhibitors (ACEi) in secondary prevention after a Non-ST-Elevation Myocardial Infarction (NSTEMI) is to reduce heart failure morbidity and all-cause mortality.

• Key points:
  • ACE inhibitors have a demonstrated survival effect in post-infarction settings.
  • The addition of an angiotensin II blocker like valsartan to an ACE inhibitor does not provide further clinical benefit if the ACE inhibitor is used at an adequate dose.
  • The use of ACE inhibitors is associated with a reduction in mortality and morbidity in patients with heart failure or left ventricular systolic dysfunction after a myocardial infarction.
  • The evidence suggests that ACE inhibitors should be used as part of the treatment regimen for secondary prevention after a NSTEMI, but the addition of other agents like angiotensin II blockers should be considered on a case-by-case basis 2.

From the Research

Role of ACE Inhibitors in Secondary Prevention after NSTEMI

• ACE inhibitors play a crucial role in secondary prevention after a Non-ST-Elevation Myocardial Infarction (NSTEMI) by reducing the risk of major cardiovascular events, such as cardiovascular death, non-fatal MI, and non-fatal ischemic stroke 3, 4, 5.
• The use of ACE inhibitors in patients with NSTEMI has been shown to improve oxidative stress, endothelial and ventricular function, and reduce ventricular remodeling as well as progression of carotid intimal and medial thickening 3.
• Current evidence suggests that ACE inhibitors should be prescribed as early as possible for all patients with acute myocardial infarction, unless contraindicated or not tolerated, and that they should be continued for at least 6 weeks; moreover, because these patients automatically qualify as high-risk individuals, indefinite therapy should be considered 3.
• The TIMI Risk Score for Secondary Prevention (TRS 2°P) score can be used to stratify post-NSTEMI patients for risk of recurrent cardiovascular events and guide the selection of more aggressive secondary prevention therapy, including the use of ACE inhibitors 6.
• ACE inhibitors are recommended as first-line therapy for secondary prevention of cardiovascular outcomes, including MI, stroke, and heart failure, in patients with NSTEMI, unless contraindicated or not tolerated 7, 4, 5.

Benefits of ACE Inhibitors

• ACE inhibitors have been shown to reduce mortality risk, decrease the progression of heart failure, and prevent arrhythmias in patients with NSTEMI 3, 4, 5.
• ACE inhibitors may also exert positive effects by modulating plasminogen activator inhibitor-1, endothelial function, and left ventricular remodeling 4.
• The use of ACE inhibitors in combination with other therapies, such as beta blockers, antiplatelet therapy, and statins, can provide additional benefits in reducing the risk of cardiovascular events in patients with NSTEMI 5.

Clinical Guidelines

• Clinical guidelines recommend the use of ACE inhibitors in all patients with NSTEMI, unless contraindicated or not tolerated, and that they should be continued indefinitely 3, 7, 4, 5.
• The choice of ACE inhibitor should be based on the individual patient's characteristics, such as the presence of heart failure, diabetes, or renal disease 7.
• Angiotensin receptor blockers (ARBs) can be used as an alternative to ACE inhibitors in patients who cannot tolerate them 7, 5.