Makindo Medical Notes

Related Subjects: |Hypertension |Chronic Heart Failure | Heart Failure and Pulmonary Oedema | Loop Diuretics | Entresto Sacubitril with Valsartan | Ivabradine | Furosemide | Angiotensin Converting Enzyme Inhibitors | Cardiac Resynchronisation Therapy (CRT) Pacemaker |

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.