====== 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.

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===== 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)

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===== Available ACE Inhibitors =====

• [[cardio:raas:lisinopril|Lisinopril]]
• [[cardio:raas:enalapril|Enalapril]]
• [[cardio:raas:captopril|Captopril]]
• [[cardio:raas:ramipril|Ramipril]]
• [[cardio:raas:benazepril|Benazepril]]
• [[cardio:raas:perindopril|Perindopril]]
• [[cardio:raas:fosinopril|Fosinopril]]
• [[cardio:raas:quinapril|Quinapril]]
• [[cardio:raas:moexipril|Moexipril]]
• [[cardio:raas:trandolapril|Trandolapril]]

Most commonly used:
• Lisinopril
• Enalapril
• Ramipril

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===== Indications =====

==== Hypertension ====
First-line therapy in many patients.

→ [[cardio:hypertension:start|Hypertension Module]]

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==== Heart Failure (HFrEF) ====

• Mortality benefit
• Reduced hospitalization
• Prevents remodeling

Core component of GDMT.

→ [[cardio:heart_failure:start|Heart Failure Module]]

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==== Post-Myocardial Infarction ====

• Prevents ventricular remodeling
• Reduces mortality

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==== Diabetic Nephropathy ====

• ↓ Intraglomerular pressure
• ↓ Proteinuria

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===== Adverse Effects =====

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

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==== Hyperkalemia ====
↓ Aldosterone → ↓ potassium excretion

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

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==== Hypotension ====
Especially first dose (volume-depleted patients)

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==== Angioedema ====
Rare but life-threatening  
More common in Black patients

Contraindication to future ACE inhibitor use.

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==== Renal Function Changes ====

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

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===== Contraindications =====

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

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===== Comparison to ARBs =====

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

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

→ [[cardio:raas:arb|Angiotensin Receptor Blockers]]

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===== 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  

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Related:

→ [[cardio:raas:arb|ARBs]]  
→ [[cardio:hf:arni|ARNI (Sacubitril/Valsartan)]]