Angiotensin Converting Enzyme Inhibitors
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ℹ️ About
- Angiotensin-Converting Enzyme Inhibitors (ACEi) are cornerstone drugs in cardiovascular and renal medicine, widely adopted in the last 20–30 years.
- They reduce morbidity and mortality in heart failure and post-myocardial infarction, and slow progression of diabetic nephropathy.
Mode of Action 🧬
- Block the conversion of angiotensin I → angiotensin II by inhibiting ACE.
- ↓ Angiotensin II → ↓ vasoconstriction, ↓ aldosterone release → reduced preload & afterload.
- ↑ Bradykinin (normally degraded by ACE) → vasodilation but responsible for cough & angioedema.
Indications 📋
- Heart failure with reduced EF (HFrEF): Improves survival, symptoms, hospitalisation rates.
- Hypertension: Especially effective in younger patients and those with diabetes/CKD.
- Post-MI: Started within 24 hours in stable patients to reduce remodelling and mortality.
- Diabetic nephropathy & CKD with proteinuria: Renoprotective by lowering intraglomerular pressure.
Dose 💊
- Start low, titrate upwards every 1–2 weeks as tolerated.
- Examples:
- Ramipril: Start 1.25–2.5 mg OD → up to 10 mg OD.
- Lisinopril: Start 2.5–5 mg OD → up to 40 mg OD.
- Always check U&E and BP before initiation and after each dose increase.
Interactions ⚠️
- NSAIDs: Triple whammy with ACEi + diuretic → acute kidney injury; ↑ risk hyperkalaemia.
- Other antihypertensives/diuretics: Additive hypotension.
- K-sparing diuretics (spironolactone, amiloride, eplerenone): Risk of severe hyperkalaemia.
- Aliskiren or ARBs: Dual blockade ↑ risk renal impairment, hyperkalaemia.
Contraindications 🚫
- History of angioedema (life-threatening swelling).
- Severe renal artery stenosis (risk of renal failure).
- Severe renal impairment (caution, but not absolute in all cases).
- Hyperkalaemia (K+ > 5.5 mmol/L).
- Pregnancy (teratogenic – fetal renal agenesis risk).
Side Effects 🩺
- Common: Dry cough (up to 20%, due to bradykinin), dizziness, hypotension, altered taste.
- Serious: Angioedema (rare but potentially fatal), renal impairment, hyperkalaemia.
- Other: Rash, pruritus, GI upset (nausea, diarrhoea, dyspepsia).
Cautions ⚠️
- Monitor renal function and potassium (baseline, 1–2 weeks after start, then periodically).
- Combination with potassium supplements or K-sparing diuretics → high risk hyperkalaemia.
- Beware initiation in elderly, dehydrated, or those on high-dose loop diuretics.
First-Dose Hypotension 💥
Patients at highest risk should be closely monitored with first dose.
- Causes: high-dose diuretics (e.g. >80 mg furosemide), hypovolaemia, SBP < 90 mmHg, hyponatraemia (<130), unstable HF, high-dose vasodilator therapy, suspected renovascular disease.
- Management: Lay patient supine with legs elevated; IV fluids if needed.
- Start at night with lowest dose, especially in elderly.
Clinical Pearls ✨
- 💡 ACEi cough: Swap to ARB (losartan, candesartan) if intolerable.
- ⚡ Heart failure: ACEi + beta-blocker + MRA = cornerstone triple therapy (now quadruple with SGLT2 inhibitors).
- ❤️ ACEi reduce afterload & improve survival → landmark trials: CONSENSUS, SOLVD (HF), HOPE (CV risk).
- 🧪 Always re-check U&E 1–2 weeks after dose change; up to 30% rise in creatinine acceptable.
