Angiotensin-converting enzyme inhibitors

Also known as

ACE inhibitors

Key examples

• Ramipril
• Lisinopril
• Perindopril

 

Common indications

1. Hypertension: for the first- or second-line treatment of hypertension, to reduce the risk of stroke, myocardial infarction and death from cardiovascular disease.
2. Chronic heart failure: for the first-line treatment of all grades of heart failure, to improve symptoms and prognosis.
3. Ischaemic heart disease: to reduce the risk of subsequent cardiovascular events such as myocardial infarction and stroke.
4. Diabetic nephropathy and chronic kidney disease (CKD) with proteinuria: to reduce proteinuria and progression of nephropathy.

 

Mechanisms of action

• ACE inhibitors block the action of the ACE, to prevent the conversion of angiotensin I to angiotensin II. Angiotensin II is a vasoconstrictor and stimulates aldosterone secretion. Blocking its action reduces peripheral vascular resistance (afterload), which lowers blood pressure. It particularly dilates the efferent glomerular arteriole, which reduces intraglomerular pressure and slows the progression of CKD. Reducing the aldosterone level promotes sodium and water excretion. This can help to reduce venous return (preload), which has a beneficial effect in heart failure.

 

Important adverse effects

• Common side effects include hypotension (particularly after the first dose), persistent dry cough (due to increased levels of bradykinin, which is usually inactivated by ACE) and hyperkalaemia (because a lower aldosterone level promotes potassium retention). They can cause or worsen renal failure. This is particularly relevant in patients with renal artery stenosis, who rely on constriction of the efferent glomerular arteriole to maintain glomerular filtration. If detected early, these adverse effects are usually reversible on stopping the drug. Rare but important idiosyncratic side effects of ACE inhibitors include angioedema and other anaphylactoid reactions.

 

Warnings

• ACE inhibitors should be avoided in patients with renal artery stenosis or acute kidney injury; in women who are, or could become, pregnant; and those who are breastfeeding. Although ACE inhibition is potentially valuable in some forms of chronic kidney disease, lower doses should be used and the effect on renal function monitored closely.

 

Important interactions

• Due to the risk of hyperkalaemia, avoid prescribing ACE inhibitors with other potassium-elevating drugs, including potassium supplements (oral or IV) and potassium-sparing diuretics except under specialist advice for advanced heart failure. In combination with other diuretics they may be associated with profound first-dose hypotension. The combination of an NSAID and an ACE inhibitor increases the risk of renal failure.