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    Angiotensin-converting enzyme inhibitors

    Angiotensin-converting enzyme inhibitors (ACE inhibitors) inhibit the conversion of angiotensin I to angiotensin II. They have many uses and are generally well tolerated. The main indications of ACE inhibitors are shown below.

    Heart failure

    ACE inhibitors are used in all grades of heart failure, usually combined with a beta-blocker .
    Potassium supplements and potassium-sparing diuretics should be discontinued before introducing an ACE inhibitor because of the risk of hyperkalaemia. However, a low dose of spironolactone may be beneficial in severe heart failure and can be used with an ACE inhibitor provided serum potassium is monitored carefully.
    Profound first-dose hypotension may occur when ACE inhibitors are introduced to patients with heart failure who are already taking a high dose of a loop diuretic (e.g. furosemide 80 mg daily or more). Temporary withdrawal of the loop diuretic reduces the risk, but may cause severe rebound pulmonary oedema.
    Therefore, for patients on high doses of loop diuretics, the ACE inhibitor may need to be initiated under specialist supervision, see below.
    An ACE inhibitor can be initiated in the community in patients who are receiving a low dose of a diuretic or who are not otherwise at risk of serious hypotension; nevertheless, care is required and a very low dose of the ACE inhibitor is given initially.

    Hypertension

    An ACE inhibitor may be the most appropriate initial drug for hypertension in younger Caucasian patients; Afro-Caribbean patients, those aged over 55 years,: and those with primary aldosteronism respond less well .
    ACE inhibitors are particularly indicated for hypertension in patients with type 1 diabetes with nephropathy They may reduce blood pressure very rapidly in some patients particularly in those receiving diuretic therapy ;
    the first dose should preferably be given at bedtime.

    Diabetic nephropathy

    . Provided there are no contra-indications, all diabetic patients with nephropathy causing proteinuria or with established microalbuminuria (at least 3 positive tests) should be treated with an ACE inhibitor or an angiotensin-II receptor antagonist, even if the blood pressure is normal; in any case, to minimise the risk of renal deterioration, blood pressure should be carefully controlled.

    Prophylaxis of cardiovascular events

    ACE inhibitors are used in the early and long-term management of patients who have had a myocardial infarction, ACE inhibitors may also have a role in preventing cardiovascular events.

    Initiation under specialist supervision

    ACE inhibitors should be initiated under specialist supervision and with careful clinical monitoring in those with severe heart failure or in those:

    receiving multiple or high-dose diuretic therapy (e.g. more than 80 mg of furosemide daily or its equivalent);

    with hypovolaemia;

    with hyponatraemia (plasma-sodium concentration below 130 mmol/litre);

    with hypotension (systolic blood pressure below 90 mmHg);

    with unstable heart failure;

    receiving high-dose vasodilator therapy;

    known renovascular disease.

    Renal effects

    Renal function and electrolytes should be checked before starting ACE inhibitors (or increasing the dose) and monitored during treatment (more frequently if features mentioned below present);

    hyperkalaemia and other side-effects of ACE inhibitors are more common in those with impaired renal function and the dose may need to be reduced .
    Although ACE inhibitors now have a specialised role in some forms of renal disease, including chronic kidney disease, they also occasionally cause impairment of renal function which may progress and become severe in other circumstances (at particular risk are the elderly).
    A specialist should be involved if renal function is significantly reduced as a result of treatment with an ACE inhibitor.

    Concomitant treatment with NSAIDs increases the risk of renal damage, and potassium-sparing diuretics (or potassium-containing salt substitutes) increase the risk of hyperkalaemia.

    In patients with severe bilateral renal artery stenosis (or severe stenosis of the artery supplying a single functioning kidney), ACE inhibitors reduce or abolish glomerular filtration and are likely to cause severe and progressive renal failure. They are therefore not recommended in patients known to have these forms of critical renovascular disease.

    ACE inhibitor treatment is unlikely to have an adverse effect on overall renal function in patients with severe unilateral renal artery stenosis and a normal contralateral kidney, but glomerular filtration is likely to be reduced (or even abolished) in the affected kidney and the long-term consequences are unknown.

    ACE inhibitors are therefore best avoided in patients with known or suspected renovascular disease, unless the blood pressure cannot be controlled by other drugs. If ACE inhibitors are used, they should be initiated only under specialist supervision and renal function should be monitored regularly.

    ACE inhibitors should also be used with particular caution in patients who may have undiagnosed and clinically silent renovascular disease. This includes patients with peripheral vascular disease or those with severe generalised atherosclerosis.

    Cautions

    ACE inhibitors need to be initiated with care in patients receiving diuretics
    first doses can cause hypotension especially in patients taking high doses of diuretics, on a low-sodium diet, on dialysis, dehydrated, or with heart failure .
    They should also be used with caution in peripheral vascular disease or generalised atherosclerosis owing to risk of clinically silent renovascular disease;
    for use in pre-existing renovascular disease, see above.

    The risk of agranulocytosis is possibly increased in collagen vascular disease (blood counts recommended).

    ACE inhibitors should be used with care in patients with severe or symptomatic aortic stenosis (risk of hypotension) and in hypertrophic cardiomyopathy.

    They should also be used with care (or avoided) in those with a history of idiopathic or hereditary angioedema.

    If jaundice or marked elevations of hepatic enzymes occur during treatment then the ACE inhibitor should be discontinued—risk of hepatic necrosis .

    Dr G Mohan.

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