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 heart failure, left ventricular dysfunction (ejection fraction <40%), hypertension, or diabetes mellitus, unless contraindicated, as stated in the 2011 ACCF/AHA focused update incorporated into the ACC/AHA 2007 guidelines 1.

Key Points

• Patients should start an ACEI within 24 hours of stabilization if they have left ventricular dysfunction, heart failure symptoms, diabetes, or hypertension.
• Common ACEIs used include lisinopril, ramipril, or perindopril, with treatment continued indefinitely as part of long-term secondary prevention.
• Start with a low dose and gradually titrate upward over 2-4 weeks to target doses as tolerated, monitoring blood pressure, renal function, and potassium levels at initiation, after dose increases, and periodically thereafter.
• ACEIs provide benefit by blocking the renin-angiotensin-aldosterone system, reducing ventricular remodeling, improving endothelial function, and decreasing cardiovascular mortality, as supported by the ACC/AHA 2008 performance measures for adults with ST-elevation and non-ST-elevation myocardial infarction 1.

Alternative Therapy

• If a patient cannot tolerate ACEIs due to cough or angioedema, an angiotensin receptor blocker (ARB) like valsartan or candesartan can be substituted as an alternative, as recommended in the 2011 ACCF/AHA focused update 1 and the ACC/AHA 2007 UA/NSTEMI guidelines 1.

Special Considerations

• Long-term aldosterone receptor blockade should be prescribed for UA/NSTEMI patients without significant renal dysfunction or hyperkalemia who are already receiving therapeutic doses of an ACE inhibitor, have an LVEF less than or equal to 0.40, and have either symptomatic HF or diabetes mellitus, as stated in the 2011 ACCF/AHA focused update 1.
• An angiotensin receptor blocker should be prescribed at discharge to those UA/NSTEMI patients who are intolerant of an ACE inhibitor and who have either clinical or radiological signs of HF and LVEF less than 0.40, as recommended in the 2011 ACCF/AHA focused update 1 and the ACC/AHA 2007 UA/NSTEMI guidelines 1.

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 Angiotensin-Converting Enzyme Inhibitors (ACEi) in Secondary Prevention

The role of Angiotensin-Converting Enzyme Inhibitors (ACEi) in secondary prevention after a Non-ST-Elevation Myocardial Infarction (NSTEMI) is supported by several studies.

• ACE inhibitors have been shown to significantly decrease the risk for cardiovascular events in patients with NSTEMI 3, 4.
• The use of ACE inhibitors in patients with heart failure and after myocardial infarction is associated with significant reductions in mortality risk 3, 4.
• ACE inhibitors should be prescribed for all patients with symptomatic congestive heart failure and for all asymptomatic patients with a left ventricular ejection fraction less than 35% to 40%, unless contraindicated or not tolerated 3.
• Data have shown that ACE inhibition improves oxidative stress, endothelial and ventricular function, and reduces ventricular remodeling as well as progression of carotid intimal and medial thickening 3.

Secondary Prevention Strategies

Secondary prevention strategies for patients with NSTEMI include:

• The use of ACE inhibitors to reduce the risk of recurrent cardiovascular events 3, 4.
• The use of the TIMI Risk Score for Secondary Prevention (TRS 2°P) score to stratify patients for risk of recurrent cardiovascular events 5.
• The consideration of indefinite therapy with ACE inhibitors for patients with NSTEMI, unless contraindicated or not tolerated 3.

Comparison with Other Therapies

Comparisons with other therapies, such as angiotensin-receptor blockade and neprilysin inhibition, have shown that ACE inhibitors remain a viable option for secondary prevention in patients with NSTEMI 6.

• The PARADISE-MI trial found that sacubitril/valsartan did not significantly decrease the risk for cardiovascular death and HF in patients with AMI complicated by left ventricular dysfunction, irrespective of the type of AMI 6.