Ramipril

Ramipril is an ACE inhibitor and the most widely prescribed antihypertensive in the UK.

It blocks the renin-angiotensin-aldosterone system by inhibiting the conversion of angiotensin I to angiotensin II, resulting in vasodilation, reduced aldosterone secretion, and decreased cardiac preload and afterload.

Ramipril is a prodrug, converted hepatically to its active metabolite ramiprilat.

It is licensed for hypertension, heart failure (post-MI and chronic), diabetic or non-diabetic nephropathy, and cardiovascular risk reduction in high-risk patients.

The HOPE trial demonstrated that ramipril 10 mg daily reduced the composite endpoint of cardiovascular death, stroke, and MI by 22% in high-risk patients, making it one of the most evidence-based ACE inhibitors for cardiovascular protection.

NICE recommends ACE inhibitors, including ramipril, as first-line for hypertension in patients under 55 (non-African/Caribbean descent), heart failure with reduced ejection fraction, and diabetic nephropathy with proteinuria.

Ramipril has a long duration of action permitting once-daily dosing for most indications.

Take ramipril once daily at the same time each day, with or without food. Swallow capsules whole with water. For heart failure, twice-daily dosing may be used during uptitration.

The first dose is often given at bedtime to mitigate first-dose hypotension, particularly in patients on diuretics or with heart failure. Continue treatment even when feeling well.

Do not discontinue without medical advice. Maintain adequate hydration. Report any persistent dry cough, facial swelling, or breathing difficulty promptly.

If undergoing anaesthesia, inform the anaesthetist that you are taking an ACE inhibitor.

Hypertension: Start 1.25-2.5 mg once daily. Usual maintenance: 2.5-5 mg once daily. Maximum: 10 mg once daily.

Heart failure (post-MI): Start 2.5 mg twice daily, titrated to 5 mg twice daily.

Chronic heart failure: Start 1.25 mg once daily, double at 1-2 week intervals. Target: 5 mg twice daily (or 10 mg once daily).

Cardiovascular prevention (HOPE regimen): Start 2.5 mg once daily, uptitrate to 10 mg once daily over 3 weeks.

Nephropathy: Start 1.25 mg once daily, titrated to 5 mg once daily.

In renal impairment (eGFR <60): start at 1.25 mg with careful titration. Monitor creatinine and potassium at each dose change.

Side effects per SmPC frequency categories.

Common (≥1/100 to <1/10): Dry cough (5-15%), headache, dizziness, fatigue, hypotension (including first-dose), nausea, diarrhoea, vomiting, rash, elevated potassium, elevated creatinine (transient, especially at initiation).

Uncommon (≥1/1,000 to <1/100): Angioedema (0.1-0.

5%), syncope, chest pain, palpitations, taste disturbance, abdominal pain, dyspepsia, dry mouth, myalgia, muscle cramps, pruritus, photosensitivity, vertigo, depression.

Rare (≥1/10,000 to <1/1,000): Hepatitis, jaundice, cholestatic liver injury, pancreatitis, Stevens-Johnson syndrome, pemphigus, vasculitis, neutropenia, agranulocytosis, anaemia (particularly in patients with renal impairment), Raynaud's phenomenon.

The dry cough is the most common reason for discontinuation and is a class effect of ACE inhibitors.

Angioedema may present as swelling of the face, lips, tongue, or larynx and requires immediate medical attention.

All warnings applicable to ACE inhibitors apply. First-dose hypotension risk is mitigated by starting at low doses and considering bedtime initiation.

Angioedema may occur at any point during treatment; the risk is higher in patients of African descent. Monitor renal function and potassium within 1-2 weeks of initiation and after dose changes.

Avoid dual RAAS blockade (ACE inhibitor + ARB + aliskiren combinations).

Ramipril is absolutely contraindicated in pregnancy — discontinue immediately if pregnancy is confirmed and switch to an alternative antihypertensive. Patients undergoing desensitisation therapy (e.

g. wasp/bee venom) or LDL apheresis with dextran sulphate membranes may experience anaphylactoid reactions while on ACE inhibitors.

The MHRA advises monitoring full blood count in patients with collagen vascular disease (e.g. SLE, scleroderma) due to the risk of neutropenia.

Ramipril is contraindicated in patients with hypersensitivity to ramipril, other ACE inhibitors, or any excipient, history of angioedema (hereditary, idiopathic, or ACE inhibitor-related), bilateral renal artery stenosis or stenosis of a solitary kidney, second and third trimester of pregnancy, haemodynamically significant aortic or mitral valve stenosis or hypertrophic cardiomyopathy, and concomitant use with aliskiren in patients with diabetes or eGFR <60 mL/min/1.

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