Angiotensin-converting enzyme (ACE) inhibitors are now the established first-line treatment in younger patients with hypertension and are also extensively used to treat heart failure. They are known to be less effective in treating hypertensive Afro-Caribbean patients. ACE inhibitors are also used to treat diabetic nephropathy and have a role in the secondary prevention of ischaemic heart disease.

Mechanism of action:

• inhibits the conversion angiotensin I to angiotensin II
  • → decrease in angiotensin II levels → to vasodilation and reduced blood pressure
  • → decrease in angiotensin II levels → reduced stimulation for aldosterone release → decrease in sodium and water retention by the kidneys
• renoprotective mechanism
  • angiotensin II constricts the efferent glomerular arterioles
  • ACE inhibitors therefore lead to dilation of the efferent arterioles → reduced glomerular capillary pressure → decreased mechanical stress on the delicate filtration barriers of the glomeruli
  • this is particularly important in diabetic nephropathy
• ACE inhibitors are activated by phase 1 metabolism in the liver

Side-effects:

• cough
  • occurs in around 15% of patients and may occur up to a year after starting treatment
  • thought to be due to increased bradykinin levels
• angioedema: may occur up to a year after starting treatment
• hyperkalaemia
• first-dose hypotension: more common in patients taking diuretics

Cautions and contraindications

• pregnancy and breastfeeding - avoid
• renovascular disease - may result in renal impairment
• aortic stenosis - may result in hypotension
• hereditary of idiopathic angioedema
• specialist advice should be sought before starting ACE inhibitors in patients with a potassium >= 5.0 mmol/L

Interactions

• patients receiving high-dose diuretic therapy (more than 80 mg of furosemide a day)
  • significantly increases the risk of hypotension

Monitoring

• urea and electrolytes should be checked before treatment is initiated and after increasing the dose
  • a rise in the creatinine and potassium may be expected after starting ACE inhibitors
  • acceptable changes are an increase in serum creatinine, up to 30% from baseline and an increase in potassium up to 5.5 mmol/l.
  • significant renal impairment may occur in patients who have undiagnosed bilateral renal artery stenosis