ACE Inhibitor Initiation and Monitoring

ACE inhibitors lower angiotensin II and raise bradykinin, and are used in hypertension, heart failure with reduced ejection fraction, after myocardial infarction with left ventricular dysfunction, diabetic and non-diabetic kidney disease with albuminuria, and high-risk vascular disease.

Treatment starts at a low dose, with checks of blood pressure, potassium and creatinine before and 1 to 2 weeks after each step.

Contraindications are previous angioedema, pregnancy, bilateral renal artery stenosis, potassium over 5.0 mmol/L at start and use within 36 hours of sacubitril valsartan.

Baseline. Record seated and standing blood pressure, creatinine, eGFR, potassium, sodium and pregnancy status, and review NSAIDs, potassium supplements, potassium-sparing diuretics and trimethoprim.

Ancestry. Angioedema and a weaker pressure response are more frequent in people of African ancestry. Cough occurs in about 1 in 10 people and is a class effect.

Ramipril. Hypertension 2.5 mg orally once daily, increased every 2 to 4 weeks to 10 mg daily. Heart failure 1.25 to 2.5 mg once daily, target 10 mg daily (or 5 mg twice daily). After myocardial infarction 2.5 mg twice daily, target 5 mg twice daily.

Lisinopril. Hypertension 10 mg orally once daily, usual 20 to 40 mg, maximum 80 mg. Heart failure 2.5 mg once daily, target 20 to 35 mg daily. Acute myocardial infarction 5 mg within 24 hours, 5 mg at 24 hours, 10 mg at 48 hours, then 10 mg daily.

Enalapril. Hypertension 5 mg orally once daily, usual 10 to 20 mg, maximum 40 mg. Heart failure 2.5 mg twice daily, target 10 to 20 mg twice daily.

First dose. Give at night. If the person is volume depleted or on a high-dose diuretic, withhold the diuretic that morning and start at half dose.

Special groups. In older adults start at half dose (ramipril 1.25 mg). In creatinine clearance under 30 mL/min start ramipril at 1.25 mg and cap at 5 mg daily, lisinopril at 2.5 mg, enalapril at 2.5 mg once daily. In dialysis, dose lisinopril and enalapril after the session. In severe hepatic impairment limit ramipril to 2.5 mg daily. In pregnancy stop at confirmation. In breastfeeding enalapril and captopril are compatible. In East Africa, once-daily generic ramipril or lisinopril is practical.

Monitoring. Check pressure, potassium and creatinine at 1 to 2 weeks after starting and after each increase, then at 3 months and every 6 to 12 months.

Acceptable change. A creatinine rise of up to 30% and potassium up to 5.5 mmol/L are accepted. Reduce the dose for potassium of 5.5 to 5.9 mmol/L and stop for 6.0 mmol/L or over, or for a creatinine rise over 30% that persists after correcting volume depletion.

Interactions. NSAIDs, potassium supplements, trimethoprim, spironolactone, lithium (raised levels) and ciclosporin. Avoid combining with an angiotensin receptor blocker.

Sick day rule. Withhold during vomiting, diarrhoea or poor intake and restart after 24 to 48 hours of normal drinking.

Stopping. Stop permanently for angioedema and do not substitute without caution, though an angiotensin receptor blocker is sometimes used under specialist advice. For cough, switch to an angiotensin receptor blocker such as losartan 50 mg once daily.

Common errors. Starting with high doses, no repeat blood test, unrecognised NSAID use, and stopping at the first creatinine rise.

Referral and escalation. Refer for a creatinine rise over 30% in the first 2 weeks (suspected renal artery stenosis), recurrent hyperkalaemia, or angioedema involving the tongue or airway, which needs urgent adrenaline and airway support.