the cornerstone
Agents that block the conversion of Angiotensin I to Angiotensin II. They are foundational therapy in heart failure, hypertension, and proteinuric kidney disease, reducing mortality and remodeling.
- Mechanism: Inhibits Angiotensin Converting Enzyme (ACE). Reduces Angiotensin II (vasoconstrictor/aldosterone stimulus) and increases Bradykinin (vasodilator).
- Dosing: Titrate to maximum tolerated dose for HFrEF benefits. Examples: Ramipril (Target 10mg), Perindopril (Target 8mg), Lisinopril (Target 20-40mg).
- PK: Renally cleared (except Fosinopril/Trandolapril mixed). Risk of accumulation in AKI.
indications
- Heart Failure (HFrEF): Mortality benefit (CONSENSUS, SOLVD).
- Hypertension: First line (esp. in diabetes/CKD).
- CKD: Reduces intraglomerular pressure (efferent vasodilation), reducing proteinuria.
- ACS: Post-MI remodeling prevention.
adverse effects
- Cough: Dry, tickly cough (5-20%) due to Bradykinin accumulation. (Switch to ARBs).
- Angioedema: Life-threatening swelling (Bradykinin). Contraindication to rechallenge.
- Hyperkalemia: Due to reduced aldosterone.
- Hemodynamic AKI: “Permissive” rise in Cre up to 30% acceptable if K+ stable.