2.5.5.1 Angiotensin-converting enzyme inhibitors

Hypertension and Heart Failure
ChoiceDrugDosage
1st choicesLisinopril tablets 2.5mg, 5mg, 10mg, 20mg

Dose:
Hypertension, initially 10mg daily, usual maintenance 20mg daily, usual maximum dose 40mg, If used in addition to diuretic or in cardiac decompensation or in volume depletion, initially 2.5-5mg once daily

Heart failure (with a diuretic), initially 2.5mg daily (under close medical supervision), increased in steps no greater than 10mg at intervals of at least 2 weeks up to max 35mg once daily if tolerated

Or
Perindopril (erbumine) tablets 2mg, 4mg, 8mg

Dose:
Hypertension, initially 4mg once daily in the morning for one month, subsequently adjusted according to response; max 8mg daily. If used in addition to diuretic, in elderly, in renal impairment, in cardiac decompensation, or in volume depletion, initially 2mg once daily

Heart failure (adjunct), initially 2mg once daily in the morning under close medical supervision, increased after at least 2 weeks to max 4mg once daily if tolerated

Or
Ramipril capsules 1.25mg, 2.5mg, 5mg, 10mgDose:
Hypertension, initially 1.25-2.5mg once daily, increased at intervals of 2-4 weeks to maximum 10mg once daily

Heart failure (adjunct), initially 1.25mg once daily under close medical supervision increased gradually at intervals of 1-2 weeks to max 10mg daily if tolerated (preferably taken in 2 divided doses)

Secondary Prevention
ChoiceDrugDosage
1st choicesPerindopril (erbumine) tablets 2mg, 4mg, 8mgDose: Following myocardial infarction or revascularisation, initially 4mg once daily in the morning increased after 2 weeks to 8mg once daily if tolerated. Elderly: 2mg once daily for 1 week, then 4mg once daily for 1 week, thereafter increased to 8mg once daily if tolerated
Or
Ramipril capsules 1.25mg, 2.5mg, 5mg, 10mgDose: Prophylaxis of cardiovascular events, initially 2.5mg once daily, increased after 1-2 weeks to 5mg once daily, then increased after a further 2-3 weeks to 10mg once daily

Prescribing Notes

  • Refer to NICE NG136 – Hypertension in adults: diagnosis and management – August 2019.
  • In heart failure, ACE inhibitors have been shown to improve symptoms and prolong life. They also improve outcome after myocardial infarction, particularly in patients with left ventricular dysfunction.
  • First dose hypotension may occur when ACE inhibitors are introduced to patients who are already receiving diuretics. Temporary withdrawal of the diuretic may reduce this risk (see BNF).
  • Monitoring is required for all patients. Patient should have their electrolytes and renal function (creatinine and eGFR) checked:
    • before initiating treatment
    • within 2 weeks of commencing treatment
    • within 2 weeks of last dose increase
    • annually
  • Treatment with ACE inhibitors can be initiated in the community but close medical supervision is required. ACE inhibitors should be initiated under specialist supervision and with careful monitoring in those with severe heart failure or in those with a number of co-morbidities (see BNF).
  • ACE inhibitors tend to cause potassium retention. To avoid dangerous hyperkalaemia, potassium supplements or potassium-sparing diuretics should not be used with ACE inhibitors. If spironolactone is prescribed, serum potassium must be monitored.
  • Cough is common in heart failure. ACE inhibitors cause cough in some patients. Do not rule out an ACE inhibitor until you are certain it is causing the cough.
  • ACE inhibitors and ARBs are contra-indicated in pregnancy and should be avoided in patients who become pregnant.
  • In hypertension associated with diabetes, ACE inhibitors are the drugs of first choice. They reduce proteinuria and slow the deterioration in renal function.
  • Every patient with heart failure as a result of left ventricular systolic dysfunction and who has no contra-indications should be prescribed an ACE inhibitor.
  • Prescribe perindopril as perindopril erbumine rather than perindopril arginine.
  • In patients who are intolerant of ACE inhibitors, an ARB may be considered as an alternative (see section 2.5.5.2).
  • For the prescribing of sacubitril/valsartan (Entresto) refer to NICE TA388. Treatment with sacubitril valsartan should be started by a heart failure specialist with access to a multidisciplinary heart failure team. Dose titration and monitoring should be performed by the most appropriate team member as defined in NICE NG106 Chronic heart failure in adults.

Cautions

  • Patients taking ACE inhibitors or ARBs should be informed that they are at an increased risk of acute kidney injury if they develop an illness associated with hypovolaemia and hypotension. ACE inhibitors and ARBs should be stopped temporarily.
  • As elderly patients are at particular risk of renal impairment, renal function should be monitored pre-treatment in patients taking ACE inhibitors. Regular U&E checks may be needed after initiation.
  • ACE inhibitors should be used with care or avoided in aortic stenosis or outflow tract obstruction.
  • Caution is required in patients who may have renovascular disease. ACE inhibitors are contra-indicated in patients with renal artery stenosis.