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starting ACE inhibitor treatment in primary care

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This section of the datatabase provides some brief guidance with respect to use of ACE inhibitors (particularly with respect to use in heart failure).

Evidence from clinical trials demonstrates that patients with heart failure, due to left ventricular dysfunction, show an improvement in symptom control and a reduction in morbidity and mortality when treated with an ACE inhibitor (ACEI). Therefore, all patients diagnosed with heart failure due to left ventricular systolic dysfunction (ejection fraction <=40%) should be considered for an ACEI

Contraindications include:

  • Haemodynamically relevant bilateral renal artery stenosis
  • Renal artery stenosis in a single functioning kidney
  • Aortic or mitral valve stenosis or outflow obstruction - except under specialist supervision
  • Known hypersensitivity to ACEI or excipients or to any other ACEI
  • History of angioedema of any cause
  • Pregnancy
  • Baseline potassium > 5.5 mmol/L

Cautions include:

  • Symptomatic or severe asymptomatic hypotension (systolic blood pressure (BP)< 90mmHg)
  • Patients with a documented intolerance of ACEI due to symptomatic hypotension - consider re-challenging with a longer acting ACEI (such as ramipril)
  • Patients on high dose diuretics (i.e. furosemide > 80mg daily) - increased risk of hypotension and renal dysfunction
  • Breastfeeding - seek specialist advice
  • Moderate to severe renal impairment: creatinine > 150ìmol/L or eGFR < 50ml / min. See individual SPCs for dose adjustment requirements
  • Baseline potassium > 5 to 5.5mmol/l

Seek specialist advice prior to initiation

  • Hypertrophic cardiomyopathy
  • Hyponatraemia (serum Na <135mmol/L)
  • Symptomatic or severe asymptomatic hypotension (systolic BP<90mmHg)
  • Significant renal dysfunction/renovascular disease e.g. creatinine > 150 micromol/L or eGFR < 50ml/min or hyperkalaemia (serum K>5.0mmol/L)
  • Renovascular disease (diagnosed as well as undiagnosed and clinically silent disease) e.g. PAD or severe generalised atherosclerosis
  • Patients undergoing dialysis/extracorporeal treatments or having desensitisation with wasp or bee venom

Initiation and monitoring

  • Check baseline blood chemistry. (e.g. serum creatinine, urea, potassium, sodium and eGFR) and blood pressure (BP)
  • Discontinue potassium supplements/potassium sparing diuretics (with the exception of aldosterone antagonists) and review need for concomitant nephrotoxic drugs e.g. NSAIDs
  • Review dose of diuretic therapy to the minimum necessary to control oedema
  • Start with the lowest recommended dose of ACEI and titrate as suggested below. Aim for the target dose, failing that, the maximum tolerated dose. Some ACEI is better than no ACEI

Dose titration

  • BP and blood chemistry (e.g. serum creatinine, urea, potassium, sodium and eGFR) should be checked within two weeks of initiation and any change of dose. Recheck at 1, 3, and 6 months after achieving maintenance dose, then at least 6 monthly thereafter. More frequent monitoring may be required especially if patients are on combined loop and thiazide diuretic therapy, or are taking aldosterone antagonists. Reduce dose/stop according to 'worsening renal function' and 'symptomatic hypotension'
  • ACEI dose should be doubled at no less than 2 weekly intervals (if approporiate) - smaller dose increments may be more clinically suitable for certain patients
  • Licensed ACI Starting dose (mg) Target dose (mg)
    Ramipril 1.25mg per day 5mg twice daily or 10mg once daily
    Lisinopril 2.5mg-5mg once daily 30-35mg once daily
    Enalapril 2.5mg twice daily 10-20mg twice daily
  • Ramipril and lisinopril are the ACEI of choice for heart failure, however some patients will require titration of existing ACEI therapy.


  • NICE advises that ACEI (or ARBs) should be initiated under specialist supervision in patients with plasma creatinine concentration above 150 µmol/L

  • at what level of deterioration in GFR or creatinine concentration rise should specialist advice be sought:
    • it has been recommended that discussion with a specialist if a patient's serum creatinine concentration rises by 30% or whose estimated GFR falls by 20% as an apparent consequence of ACEI/ARB use (2)
    • NICE have stated, with respect to use of ACE inhibitors in CKD
      • stop renin-angiotensin system antagonists if the serum potassium concentration increases to 6.0 mmol/litre or more and other drugs known to promote hyperkalaemia have been discontinued
      • following the introduction or dose increase of renin-angiotensin system antagonists, do not modify the dose if either the GFR decrease from pretreatment baseline is less than 25% or the serum creatinine increase from baseline is less than 30%
      • if there is a decrease in eGFR or increase in serum creatinine after starting or increasing the dose of renin-angiotensin system antagonists, but it is less than 25% (eGFR) or 30% (serum creatinine) of baseline, repeat the test in 1-2 weeks. Do not modify the renin-angiotensin system antagonist dose if the change in eGFR is less than 25% or the change in serum creatinine is less than 30%


  1. NHS - South London Cardiovascular and Stroke Network (accessed May 13th 2014). Prescribing ACE Inhibitors for patients with heart failure due to left ventricular dysfunction
  2. The Renal Association (May 2006).UK CKD Guidelines
  3. NICE (2010). Chronic heart failure Management of chronic heart failure in adults in primary and secondary care.
  4. NICE (July 2014). Chronic kidney disease early identification and management of chronic kidney disease in adults in primary and secondary care