What are Angiotensin-Converting Enzymes (ACE)?

From the Guidelines

Angiotensin-converting enzyme (ACE) inhibitors are recommended as a first-line treatment for patients with heart failure with reduced ejection fraction (HFrEF) to reduce morbidity and mortality, as evidenced by the 2017 ACC/AHA/HFSA guideline update 1. The use of ACE inhibitors has been consistently shown to reduce morbidity and mortality in patients with HFrEF, with or without coronary artery disease, and is beneficial for patients with prior or current symptoms of chronic HFrEF 1. Some key points to consider when using ACE inhibitors include:

• Starting at low doses and titrating upward to doses shown to reduce the risk of cardiovascular events in clinical trials 1
• Giving with caution to patients with low systemic blood pressures, renal insufficiency, or elevated serum potassium (>5.0 mEq/L) 1
• Monitoring for potential side effects such as angioedema, cough, and hyperkalemia 1
• Avoiding use during pregnancy due to risk of fetal harm 1
• Using cautiously in patients with bilateral renal artery stenosis or advanced kidney disease 1 Alternatively, angiotensin receptor blockers (ARBs) or angiotensin receptor-neprilysin inhibitors (ARNIs) may be considered for patients who are intolerant to ACE inhibitors, as they have also been shown to reduce morbidity and mortality in patients with HFrEF 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY 12. 1 Mechanism of Action Lisinopril inhibits angiotensin-converting enzyme (ACE) in human subjects and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. CLINICAL PHARMACOLOGY Mechanism of Action Enalapril, after hydrolysis to enalaprilat, inhibits angiotensin-converting enzyme (ACE) in human subjects and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II.

Angiotensin-Converting Enzymes (ACE) are inhibited by both lisinopril and enalapril.

• The mechanism of action involves the inhibition of ACE, which is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to angiotensin II.
• Angiotensin II is a vasoconstrictor substance that also stimulates aldosterone secretion by the adrenal cortex.
• The inhibition of ACE results in decreased plasma angiotensin II, leading to decreased vasopressor activity and decreased aldosterone secretion 2 3.

From the Research

Angiotensin Converting Enzymes Overview

• Angiotensin-converting enzyme (ACE) inhibitors are a class of medications used to treat hypertension and heart failure, among other conditions 4, 5, 6.
• They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, thereby relaxing blood vessels and reducing blood pressure 5.

Mechanism of Action and Effects

• ACE inhibitors also inhibit the breakdown of bradykinin, a vasodilator, which contributes to their blood pressure-lowering effect 5.
• The use of ACE inhibitors can be limited by idiosyncratic reactions, such as cough or angioedema, hyperkalemia, or hypotension 5.
• ACE inhibitors have been shown to reduce mortality in patients with heart failure and after myocardial infarction 7.

Comparison with Other Medications

• ACE inhibitors have been compared to angiotensin II receptor antagonists (ARBs) in several studies, with mixed results 7, 8.
• While ACE inhibitors and ARBs have similar efficacy in reducing blood pressure and improving outcomes, ARBs may have a more favorable side effect profile, with lower rates of cough and angioedema 8.
• However, ACE inhibitors remain a viable option for patients who cannot tolerate ARBs or have specific indications for their use 8.

Clinical Use and Guidelines

• Most guidelines recommend ACE inhibitors as first-line therapy for patients with hypertension and compelling indications, such as heart failure or diabetes 8.
• However, some studies suggest that ARBs may be a suitable alternative for patients who are intolerant of ACE inhibitors or have specific contraindications 8.
• The choice of medication ultimately depends on individual patient factors, including medical history, comorbidities, and potential side effects 8.