14. Angiotensin-converting enzyme (ACE) inhibitors

indications

• ➊

  Hypertension: for first- or second-line treatment of hypertension, to reduce the risk of stroke, myocardial infarction, and death from cardiovascular disease.

• ➋

  Chronic heart failure: for first-line treatment of all grades of heart failure, to improve symptoms and prognosis.

• ➌

  Secondary prevention of major adverse cardiovascular events in people with ischaemic heart disease, cerebrovascular disease, or peripheral vascular disease.

• ➍

  Diabetic nephropathy and chronic kidney disease (CKD) with proteinuria: to reduce proteinuria and progression of nephropathy

drugs included-3

ramipril, lisinopril, perindopril

moa

• ACE inhibitors inhibit the action of angiotensin-converting enzyme (ACE), reducing 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 (BP). It particularly dilates the efferent glomerular arteriole, which reduces intraglomerular pressure and slows the progression of CKD.

• Reducing aldosterone concentration promotes sodium and water excretion. This can help to reduce venous return (preload), which has a beneficial effect in heart failure

interactions

• Due to the risk of hyperkalaemia, avoid prescribing ACE inhibitors with other ▲ potassium-elevating drugs, including potassium supplements, aldosterone antagonists and potassium-sparing diuretics, except under specialist advice for advanced heart failure.

• In combination with diuretics they may be associated with profound first-dose hypotension.

• The combination of an ▲ NSAID and an ACE inhibitor particularly increases the risk of nephrotoxicity

adverse effects

• Common side effects include hypotension (particularly after the first dose ), and hyperkalaemia (because a lower aldosterone level promotes potassium retention). They can cause or worsen renal failure.

• Renal artery stenosis presents a particular risk, as constriction of the efferent glomerular arteriole is required to maintain glomerular filtration. If detected early, these adverse effects are usually reversible on stopping the drug.

• Dry cough is also common and caused by increased levels of bradykinin (which is inactivated by ACE). An angiotensin receptor blocker is an alternative if this occurs.

• Rare but important side effects of ACE inhibitors include angioedema and other anaphylactoid reactions

warnings

ACE inhibitors should be avoided in ✖ renal artery stenosis and ✖ acute kidney injury; in women who are, or could become, ▲ pregnant; or who are ▲ breastfeeding. ACE inhibitors are valuable in the treatment of ▲ CKD, but lower doses should be used, and renal function monitored closely (see M onitoring )

prescription

• The starting dose varies according to the indication, generally being lower in heart failure than in other indications.

• A common choice is ramipril 1.25 mg orally daily in heart failure or nephropathy, or 2.5 mg orally daily in most other indications.

• This is titrated to a maximum of 10 mg orally daily over several weeks, according to therapeutic response, side effects, and renal function

administration

ACE inhibitors can be taken with or without food. It is best to take the first dose before bed to reduce symptomatic hypotension

communication

• Advise about common side effects such as a dry cough, and dizziness due to low blood pressure, particularly after the first dose.

• Mention that, very rarely, this medicine can cause effects similar to severe allergic reactions; they should stop taking it and seek urgent medical advice if they develop facial swelling or stomach pains.

• Emphasise the need for blood test monitoring, explaining that ACE inhibitors can upset potassium balance.

• Advise them to avoid taking over-the-counter ‘antiinflammatories’ ( NSAIDs ) due to the risk of kidney damage.

• Advise that if they develop diarrhoea or vomiting, to maintain their fluid intake, and stop the ACE inhibitor until their symptoms resolve. These ‘sick day rules’ reduce the risk of dehydration, low blood pressure, and kidney damage

monitoring and stopping

• Monitor efficacy clinically; for example, severity of breathlessness in heart failure, and blood pressure in hypertension.

• For safety, check electrolytes and renal function before starting treatment. Repeat these 1–2 weeks into treatment and after increasing the dose.

• Biochemical changes can be tolerated provided they are within certain limits. The ACE inhibitor should generally be stopped if serum creatinine rises more than 30% or the estimated glomerular filtration rate (eGFR) falls more than 25%. If serum potassium rises above 5.0 mmol/L, stop other potassium-elevating and nephrotoxic drugs (see I nteractions ). If, despite this, it remains above 5.0 mmol/L, reduce the ACE inhibitor dose. If it exceeds 6.0 mmol/L, stop the ACE inhibitor and seek expert advice.

• ACE inhibitors may be required indefinitely, but treatment aims should be reviewed regularly. For example, easing of blood pressure targets in those aged over 80 years, or who develop frailty or multimorbidity, may allow dose reduction or discontinuation