What is the role of Angiotensin-Converting Enzyme Inhibitors (ACEIs) in managing Coronary Artery Disease (CAD)?

From the Guidelines

Angiotensin-Converting Enzyme Inhibitors (ACEIs) should be used in all patients with Coronary Artery Disease (CAD) who also have diabetes and/or left ventricular systolic dysfunction, as they have been shown to reduce mortality, decrease the risk of myocardial infarction, and prevent heart failure in these patients. The use of ACEIs in CAD management is supported by several studies, including the Heart Outcomes Prevention Evaluation (HOPE) trial, which demonstrated that the ACE inhibitor ramipril reduced the incidence of cardiovascular death, myocardial infarction, and stroke in patients with CAD or other vascular disease 1.

Key Points to Consider

• ACEIs, such as lisinopril, ramipril, and enalapril, are recommended as first-line therapy for many CAD patients, particularly those with comorbid conditions like hypertension, heart failure, or diabetes.
• These medications should be initiated at lower doses and gradually titrated upward to target doses as tolerated, with treatment typically continued indefinitely as part of long-term CAD management.
• ACEIs work by blocking the conversion of angiotensin I to angiotensin II, thereby reducing blood pressure, decreasing cardiac workload, and improving endothelial function.
• They also provide cardioprotective effects by preventing ventricular remodeling and reducing atherosclerotic progression.
• Patients should be monitored for potential side effects, including hypotension, hyperkalemia, cough, and rarely angioedema, with kidney function and potassium levels checked within 1-2 weeks of initiation and periodically thereafter.

Recent Guidelines and Recommendations

The 2013 ACCF/AHA guideline for the management of heart failure recommends that ACE inhibitors be prescribed to all patients with heart failure with reduced ejection fraction (HFrEF) unless there is a contraindication 1. The guideline also emphasizes the importance of using doses that have been shown to reduce the risk of cardiovascular events in clinical trials.

Conclusion Not Applicable - Direct Answer Only

The most recent and highest quality study, which is the 2013 ACCF/AHA guideline, supports the use of ACEIs in CAD patients with diabetes and/or left ventricular systolic dysfunction. Therefore, ACEIs should be used in these patients to reduce morbidity, mortality, and improve quality of life 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY 12. 1 Mechanism of Action Lisinopril inhibits angiotensin-converting enzyme (ACE) in human subjects and animals. The beneficial effects of lisinopril in hypertension and heart failure appear to result primarily from suppression of the renin-angiotensin-aldosterone system.

The role of Angiotensin-Converting Enzyme Inhibitors (ACEIs) in managing Coronary Artery Disease (CAD) is not directly addressed in the provided drug label. Key points about ACEIs include:

• Inhibition of ACE results in decreased plasma angiotensin II
• Decreased vasopressor activity and decreased aldosterone secretion However, the label does not explicitly discuss the use of ACEIs in CAD management 2.

From the Research

Role of ACEIs in CAD

• Angiotensin-Converting Enzyme Inhibitors (ACEIs) have been established in the treatment of arterial hypertension and heart failure, and have also been used in the treatment of patients with Coronary Artery Disease (CAD) 3.
• The antiischemic effects of ACEIs may be exerted through a reduction of myocardial oxygen demand, by a reduction of angiotensin-mediated coronary vasoconstriction, by an interaction with bradykinin and the prostaglandin system, by a modulation of endothelial control of vascular tone, and by an interaction with the sympathetic nervous system 3.

Clinical Findings

• Clinical findings on potential beneficial effects of ACEIs in patients with CAD are inconsistent and controversial, with some studies showing attenuation of myocardial ischemia in hypertensive patients with CAD, while others show no benefit or even deterioration in normotensive patients with CAD 3.
• ACEIs have been proven to prevent progressive deterioration in left ventricular function and to reduce mortality in patients with left ventricular dysfunction or congestive heart failure 3, 4.
• Long-term administration of ACEIs has been associated with an improvement in survival and reduced morbidity and mortality due to major cardiovascular events in patients with asymptomatic left ventricular dysfunction after myocardial infarction 3.

Secondary Prevention

• ACEIs have been shown to improve coronary heart disease outcomes, including total and cardiovascular mortality, fatal and nonfatal myocardial infarction, heart failure, revascularization, and stroke, in diverse patient groups, including those with and without left ventricular dysfunction, and among hypertensive and non-hypertensive subjects 5, 6.
• The mode of action of ACEIs in CAD is thought to be dominated by blood pressure reduction, as well as endothelial protection, with the effect of arresting or reducing the processes of atherosclerosis 6.

Patient Selection

• Patients with CAD and left ventricular dysfunction or congestive heart failure should be treated with ACEIs, as they have been shown to have a prognostic benefit 3, 4.
• In hypertensive patients, ACEIs generally seem to attenuate myocardial ischemia, while in normotensive patients with CAD and angina pectoris but without left ventricular dysfunction, ACEIs cannot generally be recommended at present, unless the patients who may have benefit from ACEI treatment can be better defined 3.
• A high prevalence of risk factors in CAD populations, including left ventricular systolic dysfunction, diabetes, myocardial infarction, and hypertension, suggests that a significant proportion of patients may benefit from ACEI treatment 7.