What are Angiotensin-Converting Enzyme (ACE) inhibitors?

From the Guidelines

ACE inhibitors are recommended for patients with heart failure with reduced ejection fraction (HFrEF) to reduce morbidity and mortality, as stated in the 2017 ACC/AHA/HFSA guideline update 1. The use of ACE inhibitors has been shown to improve survival, symptoms, functional capacity, and reduce hospitalization in patients with moderate and severe heart failure and left ventricular systolic dysfunction 1, 2. Some key points to consider when using ACE inhibitors include:

• Starting with a low dose and titrating upward to the target dose, as recommended in the 2005 European Society of Cardiology guidelines 2
• Monitoring renal function regularly, especially in patients with past or present renal dysfunction or electrolyte disturbances 2
• Avoiding use in patients with bilateral renal artery stenosis and angioedema during previous ACE-inhibitor therapy 2
• Using angiotensin receptor blockers as an alternative in patients who develop cough or angioedema on an ACE-inhibitor 1, 2 The 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes also recommends the use of ACE inhibitors in patients with left ventricular ejection fraction (LVEF) less than 0.40 and in those with hypertension, diabetes mellitus, or stable chronic kidney disease (CKD), unless contraindicated 3. Overall, the evidence supports the use of ACE inhibitors as a first-line treatment for patients with HFrEF, with careful consideration of potential side effects and contraindications.

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. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex The beneficial effects of lisinopril in hypertension and heart failure appear to result primarily from suppression of the renin-angiotensin-aldosterone system. Inhibition of ACE results in decreased plasma angiotensin II which leads to decreased vasopressor activity and to decreased aldosterone secretion.

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 II also stimulates aldosterone secretion by the adrenal cortex The beneficial effects of enalapril in hypertension and heart failure appear to result primarily from suppression of the renin-angiotensin-aldosterone system. Inhibition of ACE results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to decreased aldosterone secretion.

DESCRIPTION Captopril is a specific competitive inhibitor of angiotensin I-converting enzyme (ACE), the enzyme responsible for the conversion of angiotensin I to angiotensin II.

Main Mechanism of Action:

• ACE Inhibition: All three drugs, lisinopril 4, enalapril 5, and captopril 6, work by inhibiting angiotensin-converting enzyme (ACE).
• Effects on Angiotensin II and Aldosterone: This inhibition leads to decreased plasma angiotensin II, resulting in decreased vasopressor activity and decreased aldosterone secretion.
• Resulting Benefits: The beneficial effects of these drugs in hypertension and heart failure appear to result primarily from suppression of the renin-angiotensin-aldosterone system.

From the Research

ACE Inhibitors Overview

• ACE inhibitors are a class of medications used to treat hypertension, heart failure, and diabetic nephropathy 7, 8, 9, 10, 11
• They work by inhibiting the conversion of angiotensin I to angiotensin II, resulting in vasodilation, natriuresis, and decreased sympathetic activity 9

Benefits and Drawbacks

• ACE inhibitors are generally well-tolerated, but can cause adverse effects such as cough and angioedema 7, 9
• They are considered first-line therapy for hypertension, heart failure, and diabetic nephropathy, but may not be suitable for all patients due to potential side effects 8, 10
• Angiotensin receptor blockers (ARBs) may offer an alternative to ACE inhibitors for patients who are intolerant to ACE inhibitors 7, 9, 10

Comparison to Other Therapies

• ACE inhibitors have been compared to ARBs in several studies, with some suggesting that ARBs may have improved tolerability and similar efficacy 7, 9
• The selection of antihypertensive therapy should be based on individual patient factors, including concomitant cardiovascular and metabolic conditions 11
• Combination therapy with ACE inhibitors and other antihypertensive agents may be effective in achieving adequate blood pressure control 11

Clinical Use

• ACE inhibitors are commonly used in the treatment of hypertension, heart failure, and diabetic nephropathy 7, 8, 9, 10, 11
• They are considered a safe option for most patients, with a favorable safety profile and absence of adverse metabolic effects 8
• Recent evidence suggests that ACE inhibitors and ARBs have an equal class of recommendation for first-line treatment of hypertension 9