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ACE Inhibitors

Angiotensin-Converting Enzyme (ACE) inhibitors block conversion of Angiotensin I → Angiotensin II and are foundational drugs in cardiovascular medicine.

Primary Effects: • ↓ Vasoconstriction • ↓ Aldosterone • ↓ Sodium retention • ↓ Remodeling • ↓ Afterload and preload

ACE inhibitors are mortality-reducing drugs in heart failure and post-MI patients.

Mechanism of Action

ACE inhibitors block:

Angiotensin I → Angiotensin II

Results:

• ↓ Angiotensin II (vasoconstrictor) • ↓ Aldosterone secretion • ↓ Sodium & water retention • ↓ Sympathetic activation • ↓ Ventricular remodeling • ↑ Bradykinin (vasodilation)

Net Hemodynamic Effect: • ↓ SVR (afterload) • Mild ↓ preload • Improved cardiac output (in HF)

Available ACE Inhibitors

• Lisinopril • Enalapril • Captopril • Ramipril • Benazepril • Perindopril • Fosinopril • <del>Quinapril, 2022</del> • Moexipril • Trandolapril

Most commonly used: • Lisinopril • Enalapril • Ramipril

Indications

Hypertension

First-line therapy in many patients.

→ Hypertension Module

Heart Failure (HFrEF)

• Mortality benefit • Reduced hospitalization • Prevents remodeling

Core component of GDMT.

→ Heart Failure Module

Post-Myocardial Infarction

• Prevents ventricular remodeling • Reduces mortality

Diabetic Nephropathy

• ↓ Intraglomerular pressure • ↓ Proteinuria

Adverse Effects

Cough

Due to ↑ bradykinin accumulation Occurs in ~5–20%

Hyperkalemia

↓ Aldosterone → ↓ potassium excretion

Risk increases with: • Renal insufficiency • Potassium-sparing diuretics • ARBs • MRAs

Hypotension

Especially first dose (volume-depleted patients)

Angioedema

Rare but life-threatening More common in Black patients

Contraindication to future ACE inhibitor use.

Renal Function Changes

• Mild ↑ creatinine expected • Significant rise suggests bilateral renal artery stenosis

Contraindications

• Pregnancy • Bilateral renal artery stenosis • History of ACE inhibitor–induced angioedema

Comparison to ARBs

ACE inhibitors: • ↑ Bradykinin • Cause cough • More angioedema

ARBs: • Block AT1 receptor directly • Do not increase bradykinin • Lower cough risk

→ Angiotensin Receptor Blockers

Clinical Pearls

✔ Mortality benefit in HFrEF and post-MI ✔ First-line in many hypertensive patients ✔ Mild creatinine rise is expected ✔ Monitor potassium ✔ Switch to ARB if persistent cough